The amino acid lysine is an agent that has been proposed for treating the clinical symptoms of recurrent herpes simplex labialis. This study examined the efficacy of long-term prophylactic lysine supplementation. Twenty-six volunteers with a history of frequently recurring herpetic lesions completed a 12-month double-blind crossovers study. The experimental group received daily oral supplements of 1,000 mg 1-lysine. Serum samples were analyzed at scheduled intervals. In most instances, members of the lysine group reported significantly fewer lesions than the control group. Similarly, those who were taken off lysine supplementation generally showed a significant increase in lesion frequency. Quantitative hematologic measurements revealed the most clinically useful relationship. Data from this sample population indicated that when a person's serum lysine concentration exceeded 165 nmol/ml there was a corresponding significant decrease in recurrence rate. Conversely, the frequency rate increased significantly as concentration levels fell below 165 nmol/ml. These results suggest that prophylactic lysine may be useful in managing selected cases of recurrent herpes simplex labialis if serum lysine levels can be maintained at adequate concentrations.