Pentazocine and tripelennamine, which have been abused in combination by humans, were evaluated for pharmacologic interactions on autonomic, behavioral, and antinociceptive measures in chronic spinal dogs. Pentazocine (0.31-5 mg/kg, IV) produced miosis, hypothermia and antinociception which was mediated by spinal and supraspinal reflexes; these effects were antagonized by naltrexone. Tripelennamine (0.63-2.5 mg/kg, IV) elicited mydriasis, hyperthermia and antinociception; these effects were not blocked by naltrexone. Tripelennamine produced antinociception only on the supraspinally-mediated skin twitch reflex. Interactions between pentazocine and tripelennamine varied depending on the response measured. Effects of both drugs on pupils were additive. Temperature effects were infra-additive, with the hyperthermic effects of tripelennamine predominating over the pentazocine hypothermia, resulting in a complete physiologic antagonism of pentazocine hypothermia. Antinociception, measured by flexor reflex depression, represented only the effect of pentazocine, whereas skin twitch reflex antinociception reflected either infra-additive or additive properties. The coadministration of nonconvulsive doses of pentazocine and tripelennamine produced seizures indicating a potentiated adverse interaction. In summary, the patterns of the pentazocine-triplennamine interactions were complex and the effects of tripelennamine could not be attributed to opioid activity.