Treatment of alopecia areata remains unsatisfactory. We decided to test if systemic therapy with inosiplex (Isoprinosine(R)), an immunomodulator could influence the disease. Thirty-two subjects with recalcitrant alopecia areata, aged 16-48 years (mean 30.3+/-5.1 years), were randomized into two treatment groups of 16 subjects each. They were assigned to receive either oral inosiplex (group 1), or placebo (group 2) on a double-blind basis. Inosiplex dosage was 50 mg/kg/day in five divided doses for 12 weeks. Of the 15 evaluable patients in group 1, 5 (33.3%) had full remission, 8 (53.3%) responded partially and 2 (13.3%) did not respond. Of the 14 evaluable patients in the placebo group, none had full remission, 4 (28.5%) responded partially and 10 (71.4%) did not respond. The therapeutic difference between patients receiving active and placebo therapy was statistically significant (?2=7.82, p<0.01). Compared with placebo, oral inosiplex showed considerable efficacy in alopecia areata with insignificant side-effects. Larger studies are required, however, before inosiplex may be recommended as an efficacious and safe alternative systemic form of therapy for recalcitrant alopecia areata.