Phase I and II clinical studies have been conducted to test the safety and potential activity of the reverse transcriptase inhibitor, dideoxycytidine (ddC), in treating human immunodeficiency virus-1-infected patients. Although ddC appears to be active in combating viral infection, as judged by its ability to decrease human immunodeficiency virus-1 p24 antigen titers and increase the number of CD4+ lymphocytes, it is also capable of causing severe peripheral neuropathy in a dose-dependent manner. The studies discussed here indicate that low-dose ddC treatment regimens substantially reduce the toxic side effects of this drug, and yet retain the ability to affect p24 antigen and CD4+ lymphocyte levels. These studies also define the window of therapeutic usefulness for ddC, and suggest that both safety and activity can be maintained during long-term, low-dose use of ddC.