We retrospectively and prospectively examined the clinical presentation, course of disease, and response to therapy in 63 patients whose mycobacterial isolates were identified as Runyon group III atypical mycobacteria. All of the patients except four had pulmonary disease similar to typical pulmonary tuberculosis. The others had scrofula or abscess. There was a male predominance and whites were slightly more frequently infected in our series. Forty-six percent of the patients were from rural Oklahoma. Skin testing and chest roentgenography were important, but culture of the organism appeared to be the only productive method of distinguishing the atypical disease from typical tuberculosis. Eighty-one percent had an associated disease. The isolates showed a very high rate of primary drug resistance, and this was reflected in the difficulty in controlling the infection.