Patients with herpes progenitalis recurring every 14--28 days were treated with levamisole 150 mg orally twice weekly in an open trial to evaluate the relationship between immunomodulation and clinical response. Eight of 12 patients studied for 4--9 months reported a decrease in the frequency of recurrences. Enhanced virus-specific lymphoproliferative responses were observed in six of eight patients reporting clinical improvement. Herpes-antigen-induced production of leucocyte migration inhibitory factor (LMIF) was similarly enhanced in these individuals. In the four patients reporting no improvement, virus-specific lymphoproliferative and LMIF-generating responses were either depressed or unchanged. No significant alterations in neutralizing antibody titers were observed in any of the patients. Alterations in virus-specific lymphocyte transformation and lymphokine generation observed in vitro thus correlate with changes in clinical course in a manner consistent with the proposed immunomodulatory function of levamisole.