We evaluated, in cell cultures, the action of a series of 19 aporphine alkaloids against Herpes simplex virus type 1 (HSV-1). On the basis of viral titre reduction, six alkaloids were found to be active. The mode of action of the three most potent inhibitors, oliverine HCl, pachystaudine, and oxostephanine, was studied. These compounds did not have any virucidal or prophylactic effect but they were shown to interfere with the viral replicative cycle. Although DNA synthesis was reduced, their exact target remains to be elucidated. In the discussion, some structure-activity relationships are considered.