The cases of four patients with hairy cell leukemia and disseminated atypical mycobacterial infection (three with M. kansasii and one with M. intracellulare) are reported. These four patients were from a population of 38 patients with hairy cell leukemia evaluated at three institutions; there was an incidence figure of 10.5%. Despite infection with very drug-resistant strains, two patients showed marked clinical improvement following aggressive multiple drug therapy. Such infection should be suspected in a patient with hairy cell leukemia who has persistent fever without an obvious source. Tissue biopsy usually led to diagnosis; urine cultures were also positive in two patients.