Plasma concentration of ganciclovir was studied prospectively in 15 AIDS patients treated for acute cytomegalovirus (CMV) retinitis. Ganciclovir was administered at a mean dose of 10.3 +/- 0.6 mg/kg/day. The mean trough plasma concentration was 0.6 +/- 0.3 mg/L (n = 24), and the mean peak concentration was 7.2 +/- 2.4 mg/L (n = 6). In 12 patients, trough concentrations were below the range that has been associated with effective treatment. Low trough concentrations were associated with treatment failure in 6 patients. Following an increase in the daily dose, improvement was observed in 4 of the 6 patients. These results suggest that low plasma ganciclovir levels are associated with the failure of therapy. Monitoring the plasma concentration of ganciclovir may thus be useful before considering the virus to be resistant to the drug or before switching from ganciclovir to foscarnet.