Summary The murine model of human cytomegalovirus infection was employed to analyse the kinetics of antibody production to murine cytomegalovirus (MCMV) structural and immediate early (IE) polypeptides following MCMV infection of genetically resistant and susceptible strains of mice. A total of 22 structural and six non-structural, IE proteins were identified. Analysis of immunoblots by densitometry identified four patterns of antibody reactivity to MCMV structural polypeptides during primary and secondary antibody responses over a period of 5 weeks post-infection (p.i.). Firstly, antibodies were strongly reactive with an 83K protein soon after infection, with levels which decreased with time; antibodies to a second group of viral proteins were also recognized soon after infection, but consistent levels of reactivity were maintained. Viral proteins that were recognized beyond day 14 p.i. or following a second MCMV infection formed the third group; the fourth group consisted of viral proteins that were detected at variable times p.i. by antisera from different mouse strains. The kinetics and intensity of the antibody response to individual viral proteins were influenced by virus dose, time p.i. and by a second MCMV infection. In addition, the genetic constitution of the host influenced the antibody response to MCMV proteins both quantitatively and qualitatively. In particular, sera from mice possessing C57BL but not BALB/c genes detected a 56K M r viral protein during seroconversion. Antibody reactivity to this protein was shown to segregate among sera from CXB mice, with a strain distribution pattern which indicated a linkage with the b locus on chromosome 4. Finally, expression of the 56K protein was detected in B10.BR but not BALB/c embryo fibroblasts in vitro, with expression being a dominant trait in (BALB/c × B10.BR) F1 embryo fibroblasts. Thus, host genes may influence the expression of this structural viral protein.