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Mycobacterium avium infections are the third most common opportunistic infection in patients with AIDS. Simian immunodeficiency virus (SIV)-infected rhesus macaques naturally acquire M. avium infections from the environment, and their clinical symptoms are similar to those observed in AIDS patients. We characterized concurrent infection with SIV and M. avium in monkeys on the basis of the growth of the bacteria in macrophages (Mφs) from rhesus macaques and the ability of M. avium to induce SIV replication and tumor necrosis factor α (TNF-α) production. The simian M. avium isolate grew significantly better than did an isolate from an AIDS patient or a chicken isolate (P = .001); it induced significantly more TNF-α production in Mφs from SIV-positive and SIV-negative monkeys than did the isolate from an AIDS patient (P = .013). No significant increase in SIV replication was seen in the M. avium isolates, and no correlation was found between increased SIV replication and increased TNF-α production. In addition, Mφs from monkeys infected with M. avium during late-stage SIV disease produced less TNF-α when stimulated with virulent M. avium.