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