One of the more difficult challenges in cytopathology may be distinguishing malignancy from reactive conditions in effusions. Furthermore, it is frequently impossible to determine the primary site of the tumor on the basis of cellular morphology alone. In the present study we sought to construct a panel of antibodies that might distinguish carcinoma of the ovary from other metastatic tumor types as well as aid in the distinction between benign and malignant effusions. One hundred twenty-four cases of effusions (80 malignant and 44 benign) were examined with seven monoclonal antibodies (MAbs) (Ber-EP4, OV-TL3, OV-TL23, ID-3, SH9, H23 and D-14). Sensitivities for the seven MAbs ranged from 11% to 75%, with specificity of 43-100%. No single antibody could reliably distinguish carcinoma from reactive conditions, but Ber-EP4 combined with H23 detected 87% of malignant effusions, with a false-positive rate of 2%. Although these antibodies did not differentiate ovarian carcinoma from other types of malignancies, when used together they are highly accurate in distinguishing benign from malignant effusions.