vol. 161, no. 4 the american naturalist april 2003 Herbivore Responses to Plant Secondary Compounds: A Test of Phytochemical Coevolution Theory Howard V. Cornell 1,* and Bradford A. Hawkins 2,† 1. Department of Biological Sciences, University of Delaware, Newark, Delaware 19711; 2. Department of Ecology and Evolutionary Biology, University of California, Irvine, California 92697 Submitted November 26, 2001; Accepted September 13, 2002; Electronically published March 21, 2003 abstract: Literature data were collected on the floristic distribution and toxicity of phytochemicals to herbivores and on herbivore spe- cialization in order to test phytochemical coevolution theory. The theory makes four predictions that can be tested with this infor- mation. Herbivores can adapt to novel, more toxic chemicals by becoming specialists, or they can become generalists but at the cost of lower feeding success on any particular host. Thus, the first two predictions are as follows: herbivores should do better on chemicals that are present in their normal host, and this pattern should be stronger for specialists than for generalists. The “escape and radia- tion” aspect of the theory holds that if a plant taxon with a novel defense chemical diversifies, the chemical will become widespread. Eventually, herbivores will adapt to and disarm it. So the third pre- diction is that more widespread chemicals are less toxic than more narrowly distributed ones. Because generalists should not do as well as specialists on chemicals disarmed by the latter, the fourth pre- diction is that the third prediction should be more true for generalists than specialists and should depend on presence/absence of the chem- ical in the normal host. Multiple regressions of toxicity (herbivore mortality and final weight) on three predictor variables (chemical presence/absence in the normal host, specialism, and chemical flo- ristic distribution) and relevant interactions were used to test these predictions. Chemical presence/absence in the normal host, the in- teraction between this variable and specialism, and chemical floristic distribution had significant effects on both measures of toxicity, sup- porting the first three predictions of the model. Support for the fourth prediction (a three-way interaction among all predictor variables) was evident for final weight but not mortality, perhaps because growth is more responsive to toxicity differences than survival. In short, the phytochemistry literature provides broad support for the phytochemical coevolution model. * E-mail: cornell@udel.edu. † E-mail: bhawkins@uci.edu. Am. Nat. 2003. Vol. 161, pp. 507–522.  2003 by The University of Chicago. 0003-0147/2003/16104-010411$15.00. All rights reserved. Keywords: apparency, bioassay, coevolution, herbivore, phytochem- ical, specialization. On-line enhancements: appendix tables. Insects evolved to feed on terrestrial plants at least 400 million years ago, and herbivores and their host plants now comprise some of the richest assemblages in terrestrial communities (Price 1980; Strong et al. 1984). Investiga- tions into how such assemblages evolved have been guided by two well-founded observations. First, most herbivorous insects are specialized to one or a few host species (Jaenike 1990; Bernays and Chapman 1994; Thompson 1994), yet there are always some generalized feeders. Second, plant secondary chemicals, which play an important role in re- stricting herbivore diets, are toxic to some herbivores and harmless to others (Dethier 1954; Fraenkel 1959). Attempts to explain these observations eventually begot the theory of phytochemical coevolution (Dethier 1954; Ehrlich and Raven 1964; Berenbaum 1983a). Its essence is that plants are selected to produce secondary chemicals in response to herbivore feeding, whereas herbivores re- spond by evolving disarming mechanisms. A by-product of this disarmament is the loss of ability to feed on other plant species. Through time, plants thus become more toxic and herbivores become more specialized. Also, plants that develop novel defenses enter a new adaptive zone and undergo phylogenetic diversification (Ehrlich and Raven 1964). The same happens to herbivores that develop novel disarming mechanisms. This so-called escape and radia- tion (Thompson 1994) may be largely responsible for driv- ing the coevolutionary process. As plant species containing a novel chemical diversify, selection for disarming mech- anisms increases. Similarly, diversification of herbivores with disarming mechanisms increases selection for new or stronger defense chemicals. The theory of phytochemical coevolution has been crit- icized on a number of points (e.g., Jermy 1976, 1984; Strong et al. 1984; Howe and Westley 1988; Futuyma and Keese 1992; Farrell and Mitter 1993; Thompson 1994). The most salient are as follows: first, although insects al-