The preoptic area (POA) is a region at the junction of the telencephalon and diencephalon of the vertebrate brain that plays an important role in many functions, including reproductive behavior and thermoregulation (Boulant, 1998; Butler and Hodos, 1996). The role of the POA in thermoregulation has been most extensively studied in mammals. This region is thought to integrate information about local brain temperature and other body temperatures and to control the level of output for a set of thermoregulatory responses that are most appropriate for the given internal and environmental temperatures (Boulant, 1998). A few studies have indicated a role for the POA in the regulation of body temperature (T b ) of non-mammalian vertebrates such as fishes (Nelson and Prosser, 1979, 1981a,b), reptiles (Cabanac et al., 1967; Khromer and Crews, 1987) and birds (Nakashima et al., 1987; Necker and Gnuschke, 1989). For amphibians, no data exist about the role of the POA in thermoregulation. Although evidence has shown that the POA is an important thermoregulatory site in some ectotherm species, the neural control of fever in these animals has received no attention. Fever is a regulated increase in T b that is often described as a rise in the thermoregulatory set point (Kluger, 1991). In mammals, fever is produced by the coordinated actions of many central nervous system (CNS) regions as an adaptive response to infection. Some preoptic neurons not only sense changes in deep body temperature but are also affected by pyrogens that act on these neurons to cause a number of physiological and behavioral responses that elevate T b (Boulant, 1998). With few exceptions, both endothermic and ectothermic vertebrates (as well as invertebrates) develop fever in response to injections of exogenous pyrogens such as lipopolysaccharide (LPS; endotoxin), viruses, Gram-positive bacteria and yeast. LPS, which is the most purified form of a compound from the cell wall of Gram-negative bacteria, usually Escherichia coli, has been extensively used to induce fever in experimental animals (for a review, see Kluger, 1991). Recently, we demonstrated that the toad Bufo paracnemis develops fever after systemic injection of LPS (Bicego-Nahas et al., 2000), but the possible sites in the CNS involved in this response have not been assessed. In the present study, we tested the hypothesis that the POA is important for the development of behavioral fever in B. paracnemis. To this end, we evaluated the effect of electrolytic lesions in the POA on preferred T b and LPS-induced behavioral fever in B. paracnemis. Materials and methods Animals Male toads (Bufo paracnemis Lutz) weighing 150–250 g were collected in the vicinity of Ribeirao Preto, Sao Paulo 3513 The Journal of Experimental Biology 205, 3513–3518 (2002) Printed in Great Britain © The Company of Biologists Limited JEB4340 The preoptic area (POA) plays an important role in fever in mammals, but the role of this region in fever in ectothermic vertebrates has never been assessed. Toads, like all ectotherms, regulate their body temperature (T b ) primarily by behavior and develop behavioral fever when injected with lipopolysaccharide (LPS). Therefore, we tested the hypothesis that the POA plays a role in the behavioral fever induced by LPS in the toad Bufo paracnemis. We made electrolytic lesions in the POA of toads (0.3 mA, 8 s) and measured preferred T b using a thermal gradient. After a period of 24 h inside the gradient chamber, control, sham-operated and lesioned toads were systemically injected with LPS (200 μg kg –1 ) or pyrogen-free saline. There was no significant effect of POA lesion in animals at their normal preferred T b . LPS caused a significant increase in preferred T b of control and sham-operated toads, but lesions in the POA abolished this response. These results indicate that the POA is an important site in the central nervous system of toads, and perhaps of all vertebrates, involved in the development of fever. Key words: behavioral thermoregulation, amphibian, Bufo paracnemis, thermoregulatory set point. Summary Introduction Discrete electrolytic lesion of the preoptic area prevents LPS-induced behavioral fever in toads Kenia C. Bicego and Luiz G. S. Branco* Department of Physiology, Dental School of Ribeirao Preto and Department of Physiology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil *Author for correspondence (e-mail: branco@forp.usp.br) Accepted 5 August 2002