We describe the clinical course of 2 HIV-positive patients in whom Mycoplasma fermentans was disseminated and persistent. We identified individuals in whom M. fermentans had been detected in a peripheral blood mononuclear cell (PBMC) or bronchoalveolar lavage (BAL) specimen. Of this group a number had archival specimens of interest: liver and/or bone marrow, taken to investigate a systemic illness, and a few had M. fermentans positive tissues. Two patients, NC and DP, had recurrent episodes of lower respiratory tract infection and fever and both had been investigated by bronchoscopy on 4 occasions. M. fermentans was detected in specimens taken 18 and 27 months apart for NC and DP respectively, and in between, and repeatedly in respiratory tract tissues of DP. Granuloma were identified in the liver of NC that was M. fermentans positive but no further evidence of opportunistic infection was found during his illness. Both patients had M. fermentans positive bone marrow specimens. Assessment of the patients' records suggested that in one patient M. fermentans may have contributed to the respiratory disease and in the other to the systemic disease.