The aims of this study were ®rstly, to investigate the expression of E-cadherin complex proteins in ovarian carcinoma cells in serous effusions and in primary and metastatic lesions; and secondly to study the value of these four proteins and calretinin, a mesothelial marker, in the differential diagnosis of ovarian carcinoma cells from reactive mesothelial cells in effusions. Sixty-seven malignant effusions and 97 corresponding primary (n=36) and metastatic (n=61) lesions were immunohistochemically stained for E-cadherin and a-, b-, and c-catenin. Staining extent and intensity were scored. Effusion specimens were additionally analysed for calretinin immunoreactivity. Membrane immunoreactivity for E-cadherin and a-, b-, and c-catenin was detected on carcinoma cells in the majority of the effusions, but rarely on reactive mesothelial cells ( p<0.001 for all markers). Calretinin immunoreactivity was con®ned to mesothelial cells ( p<0.001). An association was seen between E-cadherin and a-catenin expression, in both effusions and solid tumours, and for b-catenin in solid tumours (range p<0.001 to p=0.014). Up-regulation of all four cadherin complex proteins was seen in carcinoma cells in effusions, when compared with corresponding primary tumours (range p<0.001 to p=0.028). As with effusions, metastatic lesions showed up-regulation of a-, b-, and c-catenin when compared with primary carcinomas ( p=0.002±0.015). Carcinoma cells in effusions showed in addition elevated levels of E-cadherin when compared with metastatic lesions ( p<0.001). Staining results in effusions showed no association with effusion site, tumour type or histological grade. Immunoblotting on 29 malignant effusions con®rmed the presence of all four proteins in the majority of samples and coprecipitation of E-cadherin and b-catenin was seen in ten specimens examined. E-cadherin complex proteins are widely expressed in ovarian carcinoma cells. Together with calretinin, they form a powerful battery of markers for the cytological diagnosis of carcinoma cells in effusions. The up-regulation of E-cadherin complex proteins in serous effusions and metastatic lesions may mark an early metastatic phenotype and possibly mediates survival of tumour cells at these sites through the inhibition of apoptosis.