Synchronous serum specimens from the systemic and portal circulations of 43 patients with gastrointestinal cancer were assayed for levels of carcinoembryonic antigen, CA 19-9, and CA 125 tumor-associated antigens. The number of patients having a mean ratio of portal to systemic levels greater than 1 and the observed quantity of tumor-associated antigens were significant for carcinoembryonic antigen and CA 125 only in patients with colorectal cancer. No correlations were noted with the surgical stage of disease or with high or low (normal) levels of the three tumor-associated antigens. These findings suggest that peripheral concentrations of these antigens are in equilibrium with shedding from tumors and that hepatic clearance of a single pass does not significantly alter peripheral concentrations.