The diagnosis of malignancy in peritoneal and pleural effusions can be difficult, because activated mesothelial cells may resemble malignant cells. P53 mutations are the most frequent genetic changes in human cancer and translate into an overexpression of the p53 protein detectable by immunocytochemistry. In this study, we investigated the sensitivity and specificity of 4 different monoclonal antibodies (moAB) against p53 for the diagnosis of malignancy in effusions. We also compared p53 staining with CEA immunocytochemistry which previous work had established as a specific marker of malignancy in body cavity effusions. Normal and malignant cells from 28 benign and 52 malignant effusions (pleura and ascites) were examined by indirect immuno-alkaline phosphatase method. Four different moAB against p53 (PAB 1801, PAB 240, DO-1 and DO-7) and one moAB against CEA (CEA-84) were used. Antibodies p1801, p240 and DO-1 react with 52-75% of cases of effusions with malignant cells, but also with 38-80% of benign effusions. Only the antibody DO-7 and the CEA moAB show specificity for malignant cells reacting respectively with 20 (55%) of cases. A combination of these 2 markers does not enhance the sensitivity for the detection of tumor cells. No direct correlation between CEA and p53 immunostaining could be established. The sensitivity and specificity of staining p53 in malignant cells by immunocytochemistry depend strongly on the antibody used. Some p53 moAB are positive with reactive cells in ascites and pleural effusions. Currently, p53 staining of expressing cells does not improve the identification of malignant cells in comparison with CEA immunocytochemistry, but may help to screen for patients with p53 mutations.