The thermoregulatory effects of alpha-melanocyte stimulating hormone (MSH), its potent analog, [Nle4,D-Phe7]-alpha-MSH (NDP-MSH), and the 1-7, 4-10, and 7-13 amino acid fragments of NDP-MSH were examined by administering these substances to the anterior hypothalamic-preoptic area (AHPOA) of rats. In Experiments 1a (MSH) and 1b (NDP-MSH), animals received 0, 0.5, 1, 5, 10, or 50 pM peptide in 0.5 microliters sterile saline (n = 6/group), with core rectal temperatures being recorded 0, 10, 20, 30, 40, 50, and 60 min after injection. In Experiment 2, subjects received 5 pM NDP-MSH1-7, NDP-MSH4-10, NDP-MSH7-13, NDP-MSH, or the vehicle, 0.5 microliters sterile saline, in a counterbalanced fashion (n = 13). Results indicated a significant effect of dose for both MSH, F(5, 30) = 2.81, p = 0.03, and NDP-MSH, F(5, 30) = 4.98, p = 0.002. A Newman-Keul's analysis indicated that mean temperatures for all groups receiving MSH or NDP-MSH were significantly greater than for the group that received saline (p < 0.05). An analysis of the data from Experiment 2 indicated a significant effect of substance, F(4, 48) = 17.31, p < 0.001. Mean temperature of animals receiving NDP-MSH, the 4-10, or the 7-13 fragments, did not differ from each other but were significantly greater than mean temperatures for animals receiving sterile saline or the 1-7 fragment of NDP-MSH (p < 0.05).