Herpes simplex virus type 1 (HSV-1) and HSV-2 failed in an identical fashion to replicate and produce extensive c.p.e. [cytopathic effects] in human cell monolayer cultures exposed (8 h before infection, at infection or 8 h post-infection) to various concentrations of .DELTA.-9-tetrahydrocannabinol. Similar results were obtained with a plaque assay utilizing confluent African green monkey cells. Possible mechanisms for this antiviral activity are discussed.