The nonselective dopamine (DA) receptor agonists R(-)apomorphine (APO) and R(-)-N-n-propylnorapomorphine (NPA) elicited dose- and time-dependent hypothermia in mice with ED50 values of 300 and 18 micrograms/kg, respectively. The selective D2 agonist quinpirole (LY 171555) also elicited dose-dependent hypothermia, whereas the selective D1 agonist SKF 38393 had no effect. The selective D1 and D2 antagonists SCH 23390 (1 mg/kg) and sulpiride (200 mg/kg), respectively, did not significantly alter body temperature. The hypothermic effect of a maximal dose of NPA (0.2 mg/kg) was not blocked by SCH 23390 (1 mg/kg) but was significantly attenuated (p less than 0.001) by pretreatment with sulpiride (200 mg/kg). Pretreatment with sulpiride (200 mg/kg) produced a parallel, 40-fold shift to the right of the dose-response curve for NPA. Partial, irreversible DA receptor inactivation by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) (2 mg/kg) reduced the maximal hypothermic effect of NPA (to 49% of control) without altering its ED50. Analysis of the data indicated a linear relationship between DA receptor occupancy and hypothermic response. The results demonstrate that DA agonist-induced hypothermia in mice is mediated by D2 receptors and that there is no receptor reserved for this response.