Combination therapy for moderate to severe psoriasis is often used to enhance efficacy and minimize treatment-related side effects; however, data are limited on combination therapy with the newer biologic agents. The current study examined patients who received alefacept in combination with ultraviolet B phototherapy as part of an international, open-label study evaluating up to 3 courses of alefacept in combination with other psoriasis therapies. Physician Global Assessment [corrected] scores improved by [greater than or equal to] 1 category in 88% [corrected] of patients and by [greater than or equal to] 2 categories in 76% [corrected] of patients in course A; [corrected] corresponding response rates were 100% and 55% in Course [corrected] B, and 85% and 77% in Course [corrected] C. At week 14, a PGA of "almost clear" or "clear" was achieved by 13%, 14%, and 8% of patients in courses A, B, and C, respectively. There was no evidence of a cumulative effect on T cells after multiple courses of therapy. The combination of alefacept and ultraviolet B was well tolerated and provided improvement in psoriasis.