Seventy-two AIDS patients treated with ganciclovir for cytomegalovirus (CMV) disease were prospectively monitored for the development of drug-resistant virus. No resistant strains were found in 31 patients before therapy or among seven Culture-positive patients treated for:E;;3 months. Of 13 culture-positive patients treated for ⩾3 months, 5 excreted virus resistant (ED50, > 12 µM, or ED90, > 30 µM) to ganciclovir. Thus, 38% of patients and receiving ganciclovir for >3 months and excreting virus or, overall, 7.6% of the patients were excreting CMV resistant to the drug.