The interrelationships between the pharmacokinetics of zidovudine alone and of zidovudine plus clarithromycin were evaluated with 18 volunteers with AIDS who had no infection with Mycobacterium avium complex or clinical evidence of gastroenteritis. Patients received 200 mg of zidovudine orally every 8 h on days 1 to 4 and 1,000 mg of clarithromycin every 12 h, given 2 h apart from zidovudine, on days 2 to 4. Concentrations of zidovudine in plasma were measured at steady state both prior to (phase 1, day 1) and during (phase 2, day 4) administration of clarithromycin. Levels of clarithromycin were measured at steady state on day 4. The maximum concentrations of zidovudine in plasma were significantly different in phases 1 and 2 (616.6 and 949.0 ng/ml, respectively), as were the times to the maximum concentrations of zidovudine (2.1 and 1.0 h, respectively). However, the minimum concentrations in plasma and the areas under the concentration-time curves from 0 to 6 h did not differ on days 1 and 4. There is no significant impact on the overall bioavailability of zidovudine from the addition of clarithromycin in patients with AIDS. Clarithromycin may increase the rate of zidovudine absorption, but this is unlikely to have clinical relevance.