The efficacy of two regimens of ganciclovir therapy was evaluated in 12 infants with symptomatic congenital cytomegalovirus (CMV) infection. Virologic investigations included culture from urine, saliva, and cerebrospinal fluid, detection of CMV DNA by polymerase chain reaction, and detection of CMV class-specific antibodies (IgG, IgA, IgM) by enzyme immunoassays. Six infants were given ganciclovir, 5 mg/kg twice daily for 2 weeks (group 1); the other six infants were given 7.5 mg/kg twice daily for 2 weeks and 10 mg/kg three times weekly for 3 months (group 2). In group 1 the CMV cultures of specimens from three infants became sterile; two of these infants also had negative results on CMV DNA studies; results of culture and CMV DNA study were still positive after ganciclovir therapy in the remaining three infants. Subsequently, normal outcome was observed in only two patients. In group 2, all infants had negative CMV-culture and CMV DNA results; clinical improvement was evident in five infants, one of whom had later development of mild psychomotor retardation. In another infant, severe psychomotor retardation and hearing loss developed after transient improvement developed. These preliminary data indicate that a ganciclovir regimen including a higher dose and more prolonged therapy might be more effective in infants with symptomatic congenital CMV infection.