Adult rats maternally exposed to methadone during gestation and/or lactation were tested for thermogenic responsiveness and nociceptive thresholds following acute injections of various drugs. Hot-plate latencies were recorded initially and at 1 hr following amphetamine, chloropromazine, cocaine, diazepam, ethanol or morphine administration. Rectal temperatures were recorded initially and 1, 3 and 5 hr after administration of each of these drugs. Perinatal exposure to methadone resulted in tolerance to the thermoregulatory actions of chlorpromazine and amphetamine in at least one sex of each treatment group. However, sensitivity to thermogenic response was recorded following morphine administration in rats exposed to methadone only in utero or during both gestation and lactation. An enhanced sensitivity to nociceptive thresholds was recorded in methadone-treated rats after amphetamine, cocaine and morphine injections. These results, in concert with earlier findings of altered response to methadone challenge, suggest that perinatal exposure to methadone produces specific long-term effects on the neural mechanisms underlying thermoregulation and nociception.