Squamous cell carcinoma antigen (SCC) was measured by serum radioimmunoassay in 82 patients with primary (55) or recurrent (27) squamous carcinoma of the cervix, to determine correlation with the clinical presence of tumor and response to radiation and chemotherapy. Sixty-seven percent of those with newly diagnosed cancer and eighty-one percent of those presenting with recurrence had values above 2.5 ng/ml. In the newly diagnosed patients, 17% of those with stage I and 80% of those with stages II and above had abnormal values. Mean titers for stages I through IV were 2, 9, 19, and 144 ng/ml, respectively, confirming an association with tumor burden. Twenty-four patients underwent radiation therapy; eighteen of these had elevated pretreatment levels and were assessed for response. Titers accurately predicted regression and progression in all cases. Thirty patients received chemotherapy; twenty-seven of them had elevated pretreatment levels and were evaluable for response correlation. Titers predicted response in 96% of cases. An additional group of 20 patients successfully treated and with no evidence of disease was followed with SCC levels every 3 months. In 19 of these 20 patients (95%), the marker accurately predicted the status of disease. In 2 of these patients, who recurred while on the study, the SCC level increased before the tumor became clinically apparent. We conclude that SCC levels are useful in evaluating the response of primary and recurrent squamous cell carcinoma of the cervix to radiation and chemotherapy.