The epidemiology of testicular cancer (TC) has 2 distinguishing features. First, it has an unusual unimodal age-incidence curve which peaks about age 30, and decreases with increasing age. Second, risk of the disease has been consistently associated with a high standard of living inasmuch as it is a disease of young white men of generally higher social class in economically developed populations. These features suggest that risk may be related to relatively late age of exposure to common infectious agents resulting in damage to the developing testis. We evaluated this hypothesis in a serologic case-control study in which subjects were compared for both prevalence and level of antibody to the following agents: measles, mumps, rubella, varicella (VZV), herpes simplex (HSV), cytomegalovirus (CMV), toxoplasmosis, Chlamydia, and Mycoplasma hominis. The TC cases included 50 with seminoma, 50 with embryonal carcinoma, and 17 with other sub-classifications. There were 100 male controls of comparable age. No consistent differences were found for any of the non-herpes viruses. For VZV, cases generally had elevated titers, significantly so for the seminoma patients, relative risk (RR) = 6.3 (95% confidence interval, 3.0-13.3) adjusted for the titer distributions of HSV and CMV. For HSV, seminoma patients also had elevated titers, RR = 2.6 (1.0-6.4). The strongest association was with CMV. Patients had a higher prevalence rate than controls, RR = 2.0 (1.1-3.6), and a gradient of risk with titer level. Overall, those in the highest titer quartile had an RR of 4.9 compared to those with no antibody, with a significant trend (p = 0.0002). Since age at CMV infection is directly related to social class, these findings suggest that delayed exposure to CMV, resulting in a more severe infection, may be related to risk of TC. However, confounding by immune status of the cases or by other risk factors of TC could not be evaluated and may account for this observation.