Daily administration of ethanol (10-12 g/kg) to rats in a liquid diet resulted in tolerance to the hypothermic effects of ethanol. The rats also developed cross-tolerance to the hypothermic effect of morphine (15 and 30 mg/kg), whereas no cross-tolerance to the hyperthermic effect of morphine (5 mg/kg) was seen. Administration of morphine (30 mg/kg i.p.) for 3 days resulted in tolerance to morphine hypothermia and also cross-tolerance to ethanol-induced hypothermia. These studies fit with our hypothesis that tolerance and cross-tolerance among drugs develop to drug effects rather than to the drug per se. Therefore drugs sharing a common effect, even by different mechanisms, might show cross-tolerance for that effect.