The tumor markers CA 19-9 and CA 125 defined by the monoclonal antibodies 19-9 and OC 125 were investigated with respect to organ specificity and tumor sensitivity. Normal and tumor tissue specimens, and blood samples from 34 patients with pancreatic carcinomas, 40 with ovarian carcinomas and 39 with miscellaneous tumors were examined. CA 19-9 and CA 125 were determined by immunohistochemistry (IH) applied to sections of the tumors and adjacent normal tissues. In parallel, the antigens were measured in the patients' sera by radioimmunoassay (RIA). By means of IH CA 19-9 and CA 125 were detected in normal surface cells from many different organs. Both antigens were also found in tissue sections of various types of tumors and in the sera of the corresponding patients. Thus, organ specificity could not be demonstrated. Sensitivity of CA 19-9 was found to be high for pancreatic carcinomas, i.e., 88% of the tumors expressed the antigen shown by IH and 85% of the sera revealed concentrations above the cut-off value (greater than 37 units/ml). Evidence for CA 125 was high in ovarian carcinomas with a tissue positivity in 83% and elevated (greater than 35 units/ml) serum levels in 70% of patients. Comparing IH and RIA case by case a discrepancy was found in 14% of cases with positive IH and low serum values a vice versa. Reasons for this finding are small tumor mass not producing elevated serum levels, retention of the antigen inside the tumor cells because of defective release mechanisms demonstrable only by IH, or heterogeneity of tumors with only focal antigen expression not present in the tissue sections investigated and thus disclosable only by RIA. The relevance of immunohistochemical detection of the antigens for therapeutic planning is discussed.