As the demographics of human immunodeficiency virus (HIV) infection continue to include more African-American and Hispanic females, the prevalence of concomitant HIV infection and systemic lupus erythematosus (SLE) may increase. We describe a 36-year-old woman with a 19-year history of active SLE who, after acquiring HIV infection, developed quiescent SLE with advanced immunosuppression (CD4 cell count 10/2%). After presenting with an opportunistic infection, she began receiving highly active antiretroviral therapy. Throughout a 6-month period, highly active antiretroviral therapy resulted in suppression of her viremia, as well as a concomitant rise in her CD4 cell count. With recovery of her immune status, she presented with transverse myelitis caused by her SLE, which responded well to intravenous steroids. There have been several observations of quiescence of lupus disease activity with advanced immunosuppression in HIV patients. This is a report of the recurrence of rheumatic disease in an acquired immunodeficiency syndrome patient after the initiation of highly active antiretroviral therapy. We recommend careful observation of HIV patients for reactivation of rheumatic disease while initiating highly active antiretroviral therapy.