Adverse reactions to the standard dose (1, 200 mg/day-1, 500mg/day) of azidothymidine (AZT) are serious. An in vitro pharmacokinetic study of intracellular AZT-5'-triphosphate suggested the feasibility of a clinical trial with reduced doses of AZT. A randomized trial with reduced doses of AZT (group A ; 400mg/day, n=15, group B ; 800mg/day, n=13), was conducted enrolling 28 patients with human immunodeficiency virus infection. The effective rate of AZT on CD4+ lymphocyte counts was similar for both groups, but the duration of the effect of AZT was significantly longer in group A (p<0.05). In group B, adverse reactions were more frequently observed (p<0.01), and AZT was withdrawn or the dose was reduced more frequently (p<0.05). These results suggest that AZT at a dose of 400 mg/day is less toxic, and is more beneficial for long-term treatment. (Internal Medicine 31 : 871-876, 1992)