The effects of local application of capsaicin on the activity of single thermosensitive neurons in the anterior hypothalamic-preoptic area were studied in the urethane-anesthetized rat. Local injection of capsaicin through a cannula to the vicinity of the neurons increased the activity in 15 of 28 warm-units, decreased the activity in 2 of 4 cold-units and had no effect on 5 of 10 thermally-insensitive units. Electrophoretic application of capsaicin with the use of multibarrelled microelectrodes excited 16 of 27 warm-units, inhibited 12 of 17 cold-units and had no effect on 35 of 60 thermally-insensitive units. Progressive decreases in the responsiveness of the neurons to both capsaicin and the hypothalamic temperature were observed with repeated applications of capsaicin. Many neurons ceased firing after showing excitatory or inhibitory responses to single or repeated applications of capsaicin either by local injection or electrophoretic application. The results may explain the acute thermolytic response, as well as the subsequent decrease in responsiveness to the injection of capsaicin into the anterior hypothalamic-preoptic area, on the basis of changes in the activity of thermosensitive neurons in the anterior hypothalamic-preoptic area.