BACKGROUND Because the benefits of zidovudine (AZT) in HIV-infected individuals are small and do not last long the Delta trial was designed to test whether combinations of zidovudine with didanosine (ddl) or zalcitabine (ddC) were more effective than AZT alone in extending survival and delaying disease progression. METHODS The trial was randomised, double blind, and international. 3207 participants were allocated to either AZT (600 mg per day) alone (1055), AZT plus ddl (400 mg per day) (1080), or AZT plus ddC (2.25 mg per day) (1072). Participants either had symptoms of HIV disease (if AIDS, with a CD4 cell count of > 50 x 10(6)/L) or a CD4 count of less than 350 x 10(6)/L; 2124 had not had zidovudine before (Delta 1) and 1083 had for at least 3 months (Delta 2). RESULTS Over a median follow-up of 30 months, 699 participants died, and 936 of the 2765 without AIDS at entry developed AIDS or died. In participants who had not had AZT before, both combination regimens had substantial benefits in terms of survival (regardless of disease stage at entry); a relative reduction in mortality of 42%, compared to AZT alone (95% Cl 25% to 55%), for AZT plus ddl and of 32% (95% Cl 22% to 47%) for AZT plus ddC. In participants who had had AZT before, the addition of ddl improved survival (p = 0.05; relative reduction 23% [95% Cl 0% to 41%]) but there was no direct evidence of benefit from the addition of ddC (p = 0.47; relative reduction 9% [95% Cl--17% to 29%]). The overall difference in survival between the treatment groups was significant (p < 0.0001; a relative reduction in mortality, compared to AZT alone, of 33% (95% Cl 20% to 44%) for AZT plus ddl and 21% (95% Cl 6% to 34%) for AZT plus ddC). Benefit in terms of disease progression was seen mainly in participants not previously treated with AZT and overall. There was no unexpected toxicity from the combination treatments. CONCLUSIONS Initiation of treatment with combinations of AZT plus ddl or ddC prolongs life and delays disease progression compared with AZT alone. The addition of ddl to participants already treated with AZT also improves survival, although the benefit appears less.