We determined the pharmacokinetics of zidovudine (AZT) and its metabolite (GAZT) in HIV-infected patients with end-stage renal disease (ESRD), between dialysis sessions, and compared these to HIV-infected patients with normal renal function. Clearance of AZT in ESRD patients was not significantly different from controls. The mean serum AZT levels in ESRD patients were six times greater than the levels in normal controls at 4 h. Serum levels of GAZT were higher in ESRD patients at 90 min, and by 4 h were more than an order of magnitude greater than normal controls. If the AZT serum level is a good index of toxicity, we conclude that the currently recommended dose of 200 mg AZT three times a day is probably safe for use in HIV-infected patients with ESRD. The enterohepatic metabolism of AZT, the effect of such a dosing schedule and the effects of circulating levels of GAZT on outcomes in HIV-infected patients with ESRD must be further investigated.