This clinical trial of Transfer Factor, an immunomodulator, in the treatment of herpes simplex type I, proved this agent to be more effective as regards duration of acute phase recurrences as well as the frequency of the reappearance of relapses of this disease. The evaluation was made in 20 patients whose disease had been treated before with other therapeutic agents (including acyclovir) which permitted them to be their own controls for the comparative data obtained and submitted to statistical analysis of the two parameters mentioned, duration of the acute phase and frequency of relapses. Patients with compromised cellular immunity or with any additional disease were excluded from the study. Transfer factor, one unit, was administered subcutaneously daily for 3 to 4 days during the acute phase of the disease, and subsequently at 15-day intervals for the first 6 months; followed by a continuation of monthly injections until the termination of the study period. In six of the 20 patients there was a recurrence of the disease while receiving maintenance dosages of TF. These patients were again given the full initial dosage schedule and reinstated again with the maintenance dosage. In the initial eight patients, an immune status profile was obtained, and all results were found to be in the normal range. This was considered sufficient evidence that the criteria for the selection of patients excluded any with detectable variations in the profile of the immune status, and it was decided to eliminate this as a prerequisite for participating in the study. The results showed an important improvement in the response to transfer factor immune modulation therapy. A statistically significant reduction in the frequency of recurrences within a one month period, the Student t test gave a p = 0.0001 in TF treated patients. The average duration in days of the acute phase also showed an important difference in favor of the TF treatment. The U Mann-Whitney test gave a p = 0.0005. These results suggest that, at present, TF may be considered the therapeutic agent of choice in the treatment of herpes simplex type 1 disease.