The effect of a mycobacterial infection on AIDS disease was studied in the simian model. Monkeys were infected with the primary virulent isolate SIV/DeltaB670 and inoculated 90 days later with BCG, an attenuated strain of Mycobacterium bovis. All monkeys experienced a dramatic transient increase in plasma viremia and CCR5 expression on T lymphocytes after BCG inoculation. Only two of the four SIV+ animals had substantial proliferative responses to PPD, with poor responders developing disseminated BCG during the course of the experiment. BCG inoculation of SIV-infected long-term nonprogressor (LTNP) monkeys was also performed. Similar to the acutely infected animals, two of three LTNPs experienced increases in plasma viral levels and CCR5 expression. In the majority of animals studied, there was no accelerated progression to AIDS despite the concomitant transient stimulation of virus replication and CCR5 expression on T lymphocytes.