Twenty-five of 34 patients with alopecia totalis of at least 1 year's duration and associated defects in cell-mediated immunity completed a randomized, double-blind, placebo-controlled crossover trial of the therapeutic effect of inosiplex, a synthetic immunomodulator. Each patient received 20 weeks of treatment with inosiplex and 20 weeks with placebo in randomized order. Eleven patients were identified clinically as responders to inosiplex in terms of hair regrowth. Scalp biopsy results correlated well with drug therapy. Enhanced immune function was found in the majority of responding patients; however, statistical analysis of the results of the entire patient population revealed limited significant differences. No patient experienced adverse side effects attributable to therapy. These results show that inosiplex is a safe and effective therapy for certain patients with alopecia totalis.