Monoclonal antibody (MAb) OC125 binds to approximately 80% of epithelial ovarian cancers. Serum antigen, CA125, can be detected in these patients. 131I-OC125-F(ab')2 was injected into 5 ovarian carcinoma patients with preinjection serum levels of 150 to 9,000 CA125 U/ml. Patients received the antibody intravenously in doses ranging from 0.46 to 0.94 mg with a specific activity of approximately 2.5 mCi/mg 131I. The half-life in the circulation was approximately 30 hr and was independent of serum CA125 levels. Clearance of 131I from the circulation fitted an open, one-compartment mathematical model. Gel filtration chromatography revealed antibody-antigen complexes in sera 15 min after injection of the radiolabelled antibody. By 5 days after injection, the free form of OC125 antibody could not be detected in the serum. The rate of complex formation correlated well with the observed preinjection serum CA125 levels. This direct correlation was verified in vitro using purified CA125 antigen and radiolabelled OC125 F(ab')2 fragments. The specific effects of complex formation on tumor localization remains unclear. However, the presence of complexes should not be ignored, when planning for diagnostic imaging or immunotherapy with OC125 or other MAbs reacting with circulating antigen.