The efficacy and toxicity of topical applications of 30% idoxuridine in dimethyl sulfoxide, dimethyl sulfoxide alone, or saline in 96 recurrent and 39 first episodes of genital herpes simplex virus (HSV) infection were compared. Drug was applied to lesions four times daily for seven days. In recurrent episodes, the duration of viral shedding after beginning idoxuridine in dimethyl sulfoxide use was significantly shorter (0.6 days) than with dimethyl sulfoxide (1.4 days) or saline (2.0 days) (P less than .05). In primary episodes, viral shedding lasted 2.6 days with idoxuridine in dimethyl sulfoxide and 8.4 days with dimethyl sulfoxide or saline. Idoxuridine in dimethyl sulfoxide had no effect in recurrent or primary HSV on duration of symptoms, new lesion formation, healing time, or risk of subsequent recurrence. Complications in patients given idoxuridine in dimethyl sulfoxide included local burning, generalized contact dermatitis, and vulvar carcinoma in situ. Thirty percent idoxuridine in dimethyl sulfoxide has no effect on clinical manifestations of genital HSV infection and may be hazardous.