.DELTA.-9-Tetrahydrocannabinol (.DELTA.-9-THC) a psychoactive constituent of marihuana, suppresses humoral and cell-mediated immunity. Whether structural modification of .DELTA.-9-THC resulted in a more potent immunosuppressant agent devoid of CNS activity was determined. The ED50 for reduction of the humoral immune response of mice to sheep erythrocytes as measured by spleen plaque forming cells/106 spleen cells was 70 mg/kg for .DELTA.-9-THC. .DELTA.-8-THC, 1-methyl .DELTA.-8-THC and abnormal .DELTA.-8-THC were more potent with ED50 values of 14, 13 and 8 mg/kg, respectively. Cell-mediated immunity was evaluated by a delayed-type hypersensitivity response to sheep erythrocytes. At doses of 100 mg/kg s.c. for 4 days, the cannabinoids suppressed the delayed-type hypersensitivity response from 35 to 64%. The cannabinoids can cause immunosuppression which is not related to CNS system activity since 1-methyl .DELTA.-8-THC and abnormal .DELTA.-8-THC have minimal CNS activity.