Patients with severe psoriasis may be unresponsive to or unable to tolerate the adverse effects of traditional therapy. Thioguanine has been used to treat psoriasis, but experience is limited. Most previous studies have used daily therapy and have demonstrated significant hematologic abnormalities.To reduce the adverse effects of traditional thioguanine therapy, our study patients were treated with thioguanine with a pulse-dosing schedule of 2 to 3 times per week.Marked improvement of recalcitrant psoriasis was noted in 10 (71%) of 14 patients receiving thioguanine therapy using a pulse-dosing schedule. Maintenance dosage ranged from 120 mg twice a week to 160 mg 3 times a week. Adverse effects were minimal.Thioguanine therapy is an effective treatment for recalcitrant psoriasis. A dosing schedule of 2 or 3 times per week is recommended to minimize the potential adverse effects. Routine laboratory follow-up is suggested to screen for potential adverse effects, with special attention to bone marrow suppression.