Ca2 and Ca3 are new monoclonal antibodies of IgG1 class, directed against the Ca antigen, a mucus-type glycoprotein expressed on the surface of a wide range of malignant human cells and certain specialized normal epithelia. These antibodies were produced by immunization with purified preparations of the Ca antigen. They were tested to assess their value in the diagnosis of malignant effusions. Immuno-alkaline-phosphatase staining was used. Smears of pleural and peritoneal effusions were chosen to show: undoubted malignant cells of various types; and mesothelial cells in effusions from cases in which cancer was not in question. The Ca2 antibody, at 1 in 20 dilution of the culture supernatant, was the most specific, giving no reactions with benign mesothelial cells from any of the 35 cases tested. Malignant cells were clearly stained in 35 of 40 cases of carcinoma or mesothelioma. The staining was negative in two cases of oat cell bronchial carcinoma, and in three of four cases of carcinoma of the colon. Ca3 gave similar, but somewhat stronger, reactions with carcinoma cells, but was less specific, reacting weakly with mesothelial cells in 8 of 35 benign effusions. Because the false-negative reactions given by the Ca series of antibodies are to some extent complementary to those given by monoclonal antibodies directed against the carcinoembryonic antigen (CEA), a combination of Ca2 and anti-CEA is recommended as a most useful addition to the normal cytologic examination of effusions.