Monoclonal antibody (MCA) 44-3A6 detects a cell-surface transmembrane phosphoprotein frequently expressed by pulmonary adenocarcinoma (AC) and associated with glandular differentiation. This antibody has been found to have utility in assessing routine formalin fixed paraffin-embedded pulmonary neoplasms, as well as the cytopathological evaluation of sputum and bronchial brushings. Recently, it has been shown to be useful in cytological diagnosis of pleural effusions. This study is directed at evaluating its effectiveness in detecting immunoreactive neoplastic cells in body fluids (BF) arising in other tissues. A retrospective cohort of 57 cases was studied, consisting of 36 pleural, 19 ascitic, and 2 pericardial BF. After evaluation of Papanicolaou-stained slides, the BF specimens were immunostained with MCA 44-3A6 using the avidin-biotin-peroxidase complex (ABC) method. In 29 cases, tissue sections of the primary tumors, were also available for immunostaining with MCA 44-3A6. Results showed that 39/42 (93%) of AC BF cases were positive and 28/42 (66%) stained intensely (3-4+) with 75-100% of the AC cells staining in each case. All of the 18 benign and non-AC malignant BF were negative. The staining patterns in the tissue sections of the 29 cases that had corresponding BF samples were similar. We conclude from this study that the MCA 44-3A6 (1) is useful in detecting cells consistent with AC in BF; (2) does not stain inflammatory cells or reactive mesothelial cells, thus helping distinguish reactive from malignant BF; and (3) frequency and pattern of expression in BF parallels its expression in tissue specimens. This study confirms that this MCA is a useful adjunct tool in the cytopathological evaluation of BF.