We evaluated the utility of the CA 72-4, CEA, CA 125, CA 19-9 and CA 15-3 radioimmunoassays for the detection of tumor-associated antigens (TAAs) in effusions of malignant vs. benign origin. Fluids were obtained from 51 patients with adenocarcinomas, 27 with non-epithelial malignancies, and 68 with benign disorders. The CA 72-4 radioimmunoassay (cut-off value 8.5 U/ml) detected the TAG-72 antigen in 51% of adenocarcinoma patients' effusions, while only 1 of 68 benign specimens had an elevated TAG-72 level. Similarly, CEA levels above 5 ng/ml were found in 55% of the fluids from patients with adenocarcinoma and 3.2% of effusions from patients with benign disease. CA 19-9 (cut-off value 37 U/ml) exhibited a lower degree of sensitivity, with positive values in 23.5% of the effusions due to adenocarcinomas and in 4.5% of the effusions due to benign disease. At a cut-off value of 29 U/ml, CA 15-3 was positive in 49% of fluids from patients with adenocarcinoma and in 3.0% of the benign fluids. The CA 125 RIA failed to show any specificity using the established cut-off value of 35 U/ml, with approximately 80% of all the effusions giving positive results. The specificity of the assay was increased by using a cut-off value of 3000 U/ml, but with a substantial loss in sensitivity (23.5%). Using a combination of the CA 72-4 and CEA RIAs the sensitivity for malignant effusions was increased to 73.5%. No additional improvement in the overall sensitivity was observed when using the CA 72-4 assay in combination with assays for the other markers, except in the case of 1 effusion. We conclude that the CA 72-4 RIA, possibly in combination with other assays such as CEA, may be useful in distinguishing between adenocarcinomatous and benign effusions.