The deoxynucleoside analogues 2',3'-dideoxy-cytidine (ddC) and 3'-azido-3'-deoxythymidine (zidovudine, AZT) are active as single agents in conferring immunologic and virologic benefits in patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. Both drugs, however, produce dose-limiting toxicities. AZT is associated with unacceptable levels of bone marrow suppression, and ddC can cause painful peripheral neuropathy. The different toxicity profiles of these two drugs provide the rationale for testing them in alternating dosing combinations in an attempt to retain the antiretroviral activity of each against human immunodeficiency virus, while reducing the toxicities of both. A preliminary trial showed that 200 mg AZT given orally every four hours for seven-day periods, alternating with ddC at 0.03 mg/kg body weight orally every four hours for seven-day periods is a promising treatment regimen. An expanded multicenter study is evaluating ddC at 0.01 mg/kg and 0.03 mg/kg alternating with AZT at 200 mg in weekly or monthly periods. Weekly intermittent doses of AZT at 200 mg and ddC at 0.03 mg/kg are also being tested. The rationale and methods of the trial are discussed.