Background: Recombinant human interferon beta-1b has been recently approved for the treatment of multiple sclerosis. A significant proportion of patients treated with this medication experienced cutaneous reactions. Objective: We describe the clinical and histologic features of cutaneous reactions to recombinant human interferon beta-1b. Methods: Consecutive patients with cutaneous reactions to recombinant interferon beta-1b were evaluated clinically and by biopsy. Results: Clinical lesions varied from subtle uninflamed sclerotic dermal plaques to erythematous plaques to cutaneous ulcers at injection sites. The nonsclerotic lesions were frequently painful. The firm plaques showed fibrosis histologically, whereas nonsclerotic inflammatory lesions demonstrated a consistent pattern of vascular thrombosis. Hematologic evaluation demonstrated platelet activation in most patients with inflammatory lesions, a feature also noted before interferon treatment in some patients. Conclusion: Therapy with recombinant interferon beta-1b is associated with a spectrum of cutaneous reactions and vascular thrombosis. (J Am Acad Dermatol 1997;37:553-8.)