The observation of remission occurring in several rheumatoid arthritis (RA) patients who subsequently became infected with human immunodeficiency virus (HIV) suggested that these diseases are mutually exclusive. Subsequent case reports of progression of destructive rheumatoid arthritis, even with depleted CD4 cell counts, seemed to imply that active RA may be independent of CD4 lymphocyte number and function. We report an HIV-infected individual who developed rheumatoid arthritis, which rapidly worsened with the initiation of antiretroviral therapy. The worsening disease course correlated with the increase in CD4 cell count and with the decrease in HIV viral load, perhaps suggesting a central role for the CD4 cells in the pathogenesis of rheumatoid arthritis in this particular patient.Among the therapeutic options to consider in such a patient, indomethacin and hydroxychloroquine may offer additional benefit of inhibiting viral replication. The cautious use of methotrexate with several limitations is possible, although sulfasalazine (to which our patient responded) may be a safer option.