Twenty patients with severe psoriasis were treated with the oral administration of 5 mg/kg/day of cyclosporin A (CyA) for 12 weeks. These patients had either failed to respond to or had become unresponsive to conventional treatments including PUVA, UVB, or combinations of etretinate and PUVA or UVB. Complete clearance and marked improvement were observed in 12 (60%) and 4 patients (20%), respectively. The average score of the Psoriasis Area and Severity Index (PASI) was 26.2 before treatment, decreasing to 18.3 in 2 weeks, 8.2 in 6 weeks, and 5.1 in 12 weeks of CyA treatment. There was a tendency for patients with lower blood levels of CyA to show smaller decreases in their PASI scores. In four patients who received skin biopsies, histological improvement was noted within 10 days of treatment; epidermal thickness had decreased by 32%, intraepidermal mitoses by 66%, and parakeratosis had disappeared almost completely. No clinical side effects or alterations in laboratory values were observed that required cessation of CyA. Exacerbations of psoriasis occurred in 11 of 16 patients within 6 weeks after stopping treatment. These results suggest that CyA could be the first choice of treatment for resistant severe psoriasis.