Serum dopamine β-hydroxylase activity, a useful biochemical index of peripheral sympathetic nervous activity, was measured in rats treated with Δ9-tetrahydrocannabinol or ethanol or both substances. After 7 days of treatment with either substance, serum dopamine β-hydroxylase activity decreased significantly. Combined treatment with both agents enhanced the effects of each given alone. In rats subjected to immobilization stress, treatment with Δ9- tetrahydrocannabinol appeared to potentiate the stress-induced increase in serum enzyme activity. Treatment with ethanol, with or without Δ9-tetrahydrocannabinol, effectively blocked this increase in enzyme activity. These results show that both substances have significant effects on the sympathetic nervous system which are critically influenced by environmental setting.