The incidence of cervical cancer has been found to vary between populations. Risk factors of cervical cancer include early age at first marriage, multiple marriages and antibodies to herpes simplex virus type 2 (HSV-2). The interrelatedness of these risk factors was examined by comparing data collected from 428 cancer cases and 947 control women selected from 6 populations having standardized cervical cancer incidence rates varying from 9.3 to 85.1 per 100,000. Logistic regression analysis revealed that multiple marriages, early age at first marriage or pregnancy and HSV-2 antibodies were all associated with significant risk when all 3 factors were entered into the model. Cervical cancer incidence rates were best predicted by the occurrence of HSV-2 antibodies among control women. To further assess the relation between cervical cancer rates and HSV-2 antibody, 2,306 additional sera representing an 0.8% random sample of females over 9 years of age residing in the Republic of Panama were assayed for antibodies to the virus, and the occurrence of antibodies was correlated with invasive cervical cancer rates specific to each Province. Data from both the random sample and the other study populations yielded a linear relation between the occurrence of HSV-2 antibodies and the incidence of cervical cancer. An exception was found for women living in Herrera Province, Republic of Panama, who had a higher cancer rate than predicted by HSV-2 antibody occurrence. The data suggested that infection with HSV-2 is a co-variable of venereal factors, although a role for the virus in the genesis of a certain proportion of cervical cancers is not excluded.