Lysine has been claimed to be effective in the treatment and prevention of episodes of recurrent herpes simplex (HS) infection. We carried out a double-blind, placebo-controlled trial of oral lysine hydrochloride therapy (400 mg, three times a day) in a group of 21 patients in good general health with a history of frequently recurring infection. Using our measures of episode frequency, duration, and severity, we were unable to detect any substantial benefit of lysine therapy either as a treatment for episodes in progress or as a prophylactic drug for the prevention of recurrences. We conclude that it is unlikely that lysine improves frequently recurrent HS infections in the majority of patients.