OBJECTIVE This study was performed to raise awareness among rheumatologists about two autoimmune disorders associated with long-term minocycline therapy that can coexist in the same patient. We provide an update on the occurrence of these disorders, their main characteristics, and the current knowledge of potential pathogenic mechanisms. METHODS We searched the medical literature in English indexed in MEDLINE from 1966 through April 1998 for the term minocycline combined with each of the following: autoimmune hepatitis (AIH), chronic hepatitis, lupus, systemic lupus erythematosus (SLE), anti-myeloperoxidase (anti-MPO), arthritis, vasculitis, and toxicity. We also reviewed relevant references cited in the articles our search uncovered. RESULTS We identified over 60 minocycline-induced cases of SLE and 24 cases of minocycline-induced AIH. Both autoimmune disorders coexisted in the same patient in 12 cases reported in the literature and in one case seen at our clinic. These 13 patients were characterized by symmetrical polyarthralgias/polyarthritis, elevated liver enzymes, and positive antinuclear antibodies (ANA); they also were generally anti-histone-negative, and only two patients had perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA). After withdrawal of minocycline, their symptoms resolved, and abnormal laboratory results normalized or markedly improved. CONCLUSIONS Although data on the actual prevalence of autoimmune disorders induced by minocycline are not available, numerous case reports or small series deal with such disorders. Probable pathogenic mechanisms for each of these conditions are discussed.