The incidence of acquired immunodeficiency syndrome and the number of people infected with the human immunodeficiency virus (HIV) is likely to increase into the 1990s and perhaps beyond. Zidovudine, a 2',3'-dideoxynucleoside approved for the treatment of acquired immunodeficiency syndrome, provides immunologic, virologic, and survival benefits. However, because its hematologic toxicity can be dose-limiting, investigations are ongoing with other 2',3'-dideoxynucleosides. After zidovudine, the first of these agents to be tested was 2',3'-dideoxycytidine (ddC), the most potent inhibitor of HIV reverse transcriptase among the dideoxynucleosides tested thus far. Concentrations of ddC as low as 0.5 microM provide protection against HIV in cultured T cells (and monocytes), even at high multiplicities of infection. Like the other dideoxynucleosides, activation of ddC is dependent on intracellular phosphorylation to its 5'-triphosphate form. Efforts are under way to alter enzymatically the intracellular ratio of ddC-5'-triphosphate to deoxycytidine-5'-triphosphate, its endogenous counterpart. ddC has relatively straightforward pharmacokinetics; it has a plasma half-life of about 1.2 hours and an oral bioavailability of about 87 percent. Approximately 75 percent of the drug is excreted unchanged in the urine. Patients treated with ddC have experienced both immunologic and virologic benefit, although long-term high doses are limited by the development of painful peripheral neuropathy. Significant hematologic toxicity is not evident in most patients; low-dose regimens of ddC alone, as well as alternating or in combination with zidovudine, are being tested in an effort to retain antiviral activity while minimizing treatment toxicities.