Minocycline is an oral antibiotic widely used for the long-term treatment of acne vulgaris. Unusual side effects of this medication include two overlapping autoimmune syndromes: drug-induced lupus and autoimmune hepatitis. In addition, in a few patients livedo reticularis or subcutaneous nodules have developed in association with arthritis and serum perinuclear antineutrophil cytoplasmic antibodies (P-ANCA) during long-term minocycline therapy. We report the cases of two young women receiving long-term minocycline therapy (>3 years) in whom P-ANCA-positive cutaneous polyarteritis nodosa developed. Both patients presented with a violaceous reticulated pattern on the lower extremities. Histologic examination of biopsy specimens from a reticulated area and a subcutaneous nodule showed necrotizing vasculitis of medium-sized arteries in the deep dermis, consistent with the diagnosis of polyarteritis nodosa. The cutaneous lesions rapidly resolved on discontinuation of minocycline and initiation of prednisone therapy. A high index of suspicion and testing for antineutrophil cytoplasmic antibody in addition to the standard antinuclear antibody panel can facilitate diagnosis of minocycline-related autoimmune disorders. (J Am Acad Dermatol 2001;44:198-206.)