Mice with severe combined immunodeficiency (SCID) inoculated intraperitoneally with murine cytomegalovirus (MCMV) develop a wasting syndrome at 3-4 days and die at 6-9 days after the infection. 9-(1,3-Dihydroxy-2-propoxymethyl)guanine (DHPG, ganciclovir) and (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) were compared for their efficacy against MCMV-induced disease and mortality in SCID mice. Under all treatment conditions, i.e., administration of the test compounds for 5 consecutive days starting on the day of infection (day 0), for 5 consecutive days starting on day 4 after the infection, 2 periods of 3 consecutive days starting on day 0 and day 9 after infection, or as a single dose on day 3 before infection, HPMPC proved far superior to ganciclovir in delaying the onset of the disease and increasing the lifespan of the MCMV-infected mice.