Background: Mycobacterium xenopi is associated with pulmonary disease in patients with loss of local or general host defence. Objectives: To determine the occurrence of M. xenopi in our hospital during 1987-1992 and 1993-1996, as well as the association of M. xenopi with HIV infection in 1993-1996; to evaluate the clinical significance of M. xenopi in HIV-seropositive patients. Design: Retrospective review of charts and classification of patients based on earlier definitions derived from the American Thoracic Society. Setting: Tertiary hospital. Patients: Patients with a positive isolate of M. xenopi from January 1987 until December 1996. Main outcome measures: During 1993-1996, a significant increase in the number of patients with M. xenopi was found compared with 1987-1992. Of 25 patients, 22 were HIV-seropositive. Results: The HIV-seropositive patients were classified as having definite (n = 5), probable (n = 9) and unlikely disease (n = 8) due to M. xenopi. Symptoms, median CD4 cell count, treatment and outcome did not differ between these groups. Conclusions: M. xenopi is an emerging pathogen, especially in HIV-infected patients. The criteria of the American Thoracic Society for disease due to non-tuberculous mycobacteria do not seem applicable to M. xenopi in HIV-infected patients. We suggest that two positive cultures of M. xenopi and no other likely cause of symptoms present should be considered the criteria for diagnosis of M. xenopi disease in HIV-infected patients.