Plasma levels of carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), and human chorionic gonadotropin (hCG) were measured in 253 patients with gynecologic malignancies and in 317 patients with benign gynecologic diseases. Plasma concentrations of each of these antigens were elevated in a significantly (p less than 0.001) greater number of patients with invasive gynecologic cancers than in the control population. Carcinoembryonic antigen was the most commonly elevated marker, followed by AFP and hCG. Prior to therapy, over 85% of patients with ovarian or cervical cancer had elevated plasma levels of one or more antigens. Specifically, CEA was most often elevated in patients with mucinous adenocarcinomas of the ovary and endocervix. Alpha-fetoprotein was most often increased in patients with germ cell or stromal tumors of the ovary and in patients with large-cell nonkeratinizing cervical cancers. In contrast, hCG concentrations were highest in patients with serious cystadenocarcinomas of the ovary and in patients with keratinizing squamous cell carcinomas of the cervix. Plasma antigen levels were directly related to tumor differentiation and stage of disease, and generally returned to normal eight to 12 weeks following therapy. Effective plasma and tumor antigen screening during initial evaluation of patients with gynecologic tumors should help to identify the most appropriate antigen for immunodetection procedures and for serial plasma determinations following therapy.