d-Amphetamine increases the motor activity at a dose range of 0.5-4 mg/kg. delta(9)-Tetrahydrocannabinol (THC) diminishes this effect dose-dependently. Also, the hyperthermia caused by 5 mg/kg d-amphetamine is antagonized by THC, whereas the d-amphetamine induced stereotype movements (above 4 mg/kg) are prolonged by the cannabinoid. THC and d-amphetamine both reduce the food and water intake and the normal development body weight of rats. In combination the two substances have an additive effect. Rats treated with 5 mg/kg d-amphetamine show a significant enhancement of the dopamine (DA) concentration (26%) in the brain stem 2 h p.i. Pretreatment with 10 mg/kg THC, which also causes an increase of DA by 15%, raises the DA content by 50%. Norepinephrine (NE) in the brain stem and hypothalamus is reduced by d-amphetamine but THC has no effect on the concentration of this monoamine. After subchronical treatment with THC tolerance is demonstrable to all THC effects tested. But there is no cross tolerance between delta(9)-THC and d-amphetamine since the pharmacological as well as the biochemical effects of d-amphetamine occur despite the subchronical treatment with THC.