BACKGROUND In vivo, halothane alters spontaneous firing in and thermosensitivity of neurons in the preoptic region of the anterior hypothalamus. To better understand the mechanisms by which halothane specifically disrupts normal thermoregulation, this investigation examined the effects of halothane on thermosensitive preoptic region neurons in isolated hypothalamic tissue slices. METHODS Brain slices were obtained and prepared from Sprague-Dawley rats. Preoptic region neurons were characterized by extracellular recording of spontaneous firing rates and thermosensitivity to localized heating and cooling, before, during, and after halothane equilibrated in the perfusate and carrier gas. RESULTS One hundred sixteen neurons were characterized by their thermosensitivity as: 29% warm-sensitive (> 0.8 spikes.s-1.degrees C-1); 14% cold-sensitive (< 0.6 spikes.s-1.degrees C-1); and 57% temperature-insensitive. Halothane significantly reduced the spontaneous firing rates to 64% of control and the thermosensitivity to 55% of control for warm-sensitive neurons at 1% halothane. Halothane significantly reduced the spontaneous firing rate of cold-sensitive neurons to 24 and 40% of control, and the thermosensitivity to 61 and 36% of control at 0.5, and 1% halothane, respectively. Spontaneous firing rates and thermosensitivity returned toward control values in warm-sensitive neurons (92 and 122% of control, respectively) after discontinuation of halothane, which did not occur in cold-sensitive neurons (49 and 36% of control, respectively). Halothane did not alter the thermosensitive temperature range or the set point temperature at which neurons became most thermosensitive. Halothane also did not affect the firing rates of temperature-insensitive neurons. CONCLUSIONS Halothane alters the firing rate and thermosensitivity of individual temperature-sensitive neurons in in vitro slices of the preoptic region of the anterior hypothalamus in the absence of afferent modulation. This disruption may result in an imprecision of thermoregulatory responses locally within the preoptic region, to thermal challenges and represents a potential mechanism by which halothane widens the thermoregulatory threshold range.