In response to cold and in fever, heat dissipation from the skin is reduced by sympathetic vasoconstriction. The preoptic region has been implicated in regulating basal, thermal and febrile vasoconstriction of cutaneous vessels such as the rat's tail, but the neurons responsible for these functions have not been well localized. We recorded activity from single sympathetic nerve fibers supplying tail vessels in urethane-anaesthetised rats, while microinjections of GABA (300 mM, 15-30 nl) were used to inhibit neurons in different parts of the preoptic region. Tail fiber activity increased promptly after GABA injections in two distinct regions; a rostromedial region (RMPO) centered around the organum vasculosum of the lamina terminalis, and a second region centered ~1 mm caudolaterally (CLPO). Responses to GABA within each region were similar. The febrile mediator, prostaglandin E₂ (PGE₂ ; 0.2 or 1 ng in 15 nl) was then microinjected into GABA-sensitive preoptic sites. Injections of PGE₂ into the RMPO induced a rapid increase in tail fiber activity followed by a rise in core temperature; injections into the rostromedial part of CLPO gave delayed tail fiber responses; injections into the central and caudal parts of CLPO were without effect. These results indicate that neurons in two distinct preoptic regions provide tonic inhibitory drive to the tail vasoconstrictor supply, but febrile vasoconstriction is mediated by PGE₂ selectively inhibiting neurons in the rostromedial preoptic region.