Disseminated atypical mycobacterial infections developed in nine of 186 patients with hairy cell leukemia who were seen over 10 years at the University of Chicago Hospital. Clinically, these patients had symptoms of fever and chills; an infiltrate was usually present on chest radiography. Invasive diagnostic studies, including thoracotomy and laparotomy, were necessary for confirmation of the diagnosis of atypical mycobacteria infection. Confirmatory culture specimens were obtained from lymph nodes, liver, and splenic tissue. Six patients had infections with Mycobacterium kansasii; two with M. avium-intracellulare; and one with M. chelonei. Treatment with multiple anti-tuberculosis drugs was initiated either empirically (six patients); after obtaining pathologic evidence of granuloma or acid-fast bacilli (two patients); or after obtaining a positive culture result (one patient). Five of the nine patients survived the infection and continued taking anti-tuberculosis drugs for total periods of nine months to two years. Awareness of the association between hairy cell leukemia and atypical mycobacteria infection, with early consideration of invasive diagnostic studies, as well as empiric anti-tuberculosis therapy, may prolong the survival time for many patients with hairy cell leukemia.