We evaluated the role of mycobacteria in chronic skin manifestations. The etiologies of chronic skin disorders in 90 patients were analyzed by culture, histopathologic examination, and skin testing for mycobacteria. There were 20 clinical diagnoses; prurigo nodularis was the most common diagnosis (43 patients). Cultures were incubated at 32 degrees C and 36 degrees C for 6 months. Fourteen cultures (16%) yielded the following mycobacteria: Mycobacterium tuberculosis (5), Mycobacterium avium/Mycobacterium intracellulare complex (3), Mycobacterium malmoense (2), and other mycobacteria (4). Acid-fast bacilli were detected in 24 (28%) of the 86 histopathologic specimens examined, including nine of the 14 culture-positive specimens. Granulomatous infection was present in three specimens (3%); cultures of two of these specimens yielded M. tuberculosis, and culture of one was negative. Skin reactivity to 12 mycobacterial antigens was tested. The patients for whom staining and/or culture was positive for mycobacteria had significantly larger skin reactions to M. malmoense antigen (P < .001) than did the patients with bacteriologically negative skin disorders. There was no correlation between the species isolated and the skin reactivity to the species-specific antigen.