The efficacy of orally administered mycophenolic acid (MPA), an inhibitor of guanosine monophosphate (GMP) synthesis, for the treatment of psoriasis, was studied in a double-blind fashion. Of twenty-one patients completing the study period, ten of eleven patients treated with MPA had a greater than 25% decrease in severity score compared with only two of ten patients treated with placebo. The placebo group had a slight increase in severity score compared to almost 50% reduction in the average severity score of the MPA-treated group. After termination of the double-blind portion of the study, the placebo group was treated with MPA and showed a 60% decrease in severity score. Adverse effects encountered included anorexia, nausea, vomiting, and diarrhea. One patient had an uncomplicated episode of herpes zoster. Other than a mild decrease hemoglobin, no hematologic toxicity was noted.