We evaluated the effect of combination therapy with zidovudine (AZT) plus zalcitabine (ddC) in human immunodeficiency virus type 1 (HIV-1)-infected patients who had not previously received antiretroviral treatment ('naive' patients). The immunological and virological parameters evaluated were CD4 cell count, syncytium-inducing (SI) viral phenotype and plasma HIV-1 RNA copies/ml (HIV viral load). A total of 75 patients entered the study, with CD4 cell counts between 200 and 500 cells/mm3. All received zidovudine (200 mg) plus zalcitabine (0.75 mg) three times daily for 24 weeks. Treatment was well tolerated. However, four patients presented with anaemia (haemoglobin < 10.0 g/dl) and one patient had both anaemia and neutropenia (0.8 x 10(9) neutrophils/l). Combination therapy with zidovudine plus zalcitabine resulted in a pronounced improvement of virological and immunological markers. Approximately 25% of patients achieved undetectable plasma HIV RNA levels (< 200 copies/ml) at week 24. At the end of the study (24 weeks) a significant reduction (> 0.5 log) of plasma HIV RNA was observed in approximately 70% of patients and in 50% an even greater decrease (> 1 log) was achieved. The most significant decrease in mean plasma HIV RNA levels was observed at week 4, whereas the highest increase in CD4 cell count was found at week 24. Approximately 80% of patients who showed baseline plasma HIV RNA levels below 20000 copies/ml had less than 5000 copies/ml at week 24. The plasma HIV RNA reduction observed at week 4 was significantly maintained at week 24. Therefore, we can rapidly select those who will not respond to therapy and adjust the treatment after a short interval. Our study supports the idea of early therapy because all patients who reached undetectable levels of plasma HIV RNA at week 24 had at baseline a median plasma HIV RNA load of 2560 copies/ml. In conclusion, zidovudine in combination with zalcitabine was well tolerated in the majority of patients and led to a significant reduction in plasma HIV RNA copies in most of the patients with initial viraemia lower than 20000 copies/ml.