Significant epitopes of two of the major cytomegalovirus antigens, a nonstructural DNA-binding protein of 52 kilodaltons (kDa) and a structural phosphoprotein of 150 kDa, expressed as fusion proteins with the beta-galactosidase, were induced in Escherichia coli after infection with recombinant lambda gt11 clones. The epitopes were then used in immunoblotting to assay specific immunoglobulin G (IgG) and IgM in several groups of sera from long-term seropositive subjects and from patients undergoing primary or secondary virus infection. The data obtained showed that IgM reacting with the 52-kDa nonstructural antigen are linked to primary virus infection and can therefore be considered a serological marker of this infection.