The antibody isotype response to human cytomegalovirus (CMV) was studied in paired sera from patients with primary and recurrent CMV infection. The majority of sera was obtained from immunocompromised patients. In the 48 patients with primary CMV infection, CMV-specific IgM (CMV-IgM) and IgG (CMV-IgG) antibodies were found in all patients, and CMV-specific IgA (CMV-IgA) and IgE (CMV-IgE) antibodies in 46 patients. CMV-IgM, -IgA, and -IgE antibodies were found in, respectively, 21, 31 and 4 of the 53 patients with recurrent CMV infection, and in, respectively, 3, 3 and 1 of the healthy controls. The results indicate that CMV-IgE is a better marker of primary CMV infection than CMV-IgM, and confirm that detection of CMV-IgM and -IgA may also be useful for diagnosis of recurrent CMV infection.