Background: A variety of systemically administered drugs are used to treat psoriasis, including methotrexate, cyclosporine, acitretin, and hydroxyurea. Unfortunately, some wpatients are unresponsive to these agents. For others, side effects and cumulative toxicity prevent continued use. Objective: Our purpose is to report the results of thioguanine (6-thioguanine) treatment of 21 patients with refractory psoriasis. Methods: We conducted a retrospective review of the treatment courses of 21 patients with psoriasis who were treated with thioguanine. Daily dosing and pulse dosing were both used, from 20 mg two times a week to 120 mg daily. All patients had been treated with other systemic therapies, and the majority (86%) had been treated with methotrexate. Results: Patient outcome (response to treatment relative to baseline) was classified into 3 groups: those with more than 90% improvement, those with between 50% and 90% improvement, and those with less than 50% improvement. Outcome data were based on the patient's subjective rating of disease severity before the start of thioguanine therapy and during the entire treatment course. Of the 18 patients able to be evaluated, 14 of 18 (78%) had dramatic improvement (>90%); 3 of 18 (17%) had lesser improvement (50%-90%); and only 1 of 18 had less than 50% improvement. The mean duration of treatment was 15.5 months. The primary side effect was myelosuppression, mild in 9 of 18 (white blood cell counts ranging from 1600-3700/μL; platelet counts ranging from 90,000-122,000/μL, and hematocrit values ranging from 24%-31%), and severe in 1 of 18 (white blood cell count of 1300/μL, platelet count of 17,000/μL, and hematocrit of 20%). Conclusion: Thioguanine appears to be an effective treatment for patients with severe recalcitrant psoriasis. Myelosuppression is a significant, but easily monitored side effect that can now be more accurately predicted by determining thiopurine methyltransferase levels before starting thioguanine. Further prospective studies are needed to establish criteria, which will maximize efficacy of this drug in the treatment of psoriasis and minimize toxicity. (J Am Acad Dermatol 2001;44:67-72.)