A previous survey found the average annual age-adjusted incidence of cervical cancer in Herrera Province, Panama, to be 79/100, 000, exceeding any other reported world rate. In an effort to clarify the reasons for this excessive occurrence, a case-control study was conducted among patients diagnosed between 1974-1980. Sixty-six percent of cervical cancer patients from Herrera Province were alive and were contacted by the study team; of these 91% were successfully interviewed and provided serum specimens. The total study encompassed 156/169 surviving patients and 309 age-neighborhood matched controls. Sexual promiscuity was uncommon, but it exerted a major effect, with those reporting 4 or more life-time sex partners being at a 4-fold excess risk compared to those reporting only one partner. First intercourse at a young age was common (21% began sexual activity prior to age 16) but it failed to alter risk once number of partners was taken into account. Oral contraceptive use was associated with a 2-fold excess risk and this was not substantially affected by controlling for sexual parameters. Thirty-three percent of the study subjects had anti-herpes-simplex type-2 antibody as measured by both neutralization and radioimmunoassays. Although results of the neutralization test were not predictive of risk, women with a radioimmunoassay indicative of HSV-2 infection were at a 40% excess risk for cervical cancer after adjustment for sexual characteristics.