Aims: To examine the frequency and pattern of expression of p53 and bcl-2 in archival material from patients with cholangiocarcinomas and to evaluate their respective roles in its pathogenesis, diagnosis and prognosis. Methods and results: Twenty-eight surgical cases of cholangiocarcinomas diagnosed at St James's University Hospital and 16 control cases were immunostained with monoclonal antibodies to p53 and bcl-2 using streptavidin-biotin complex method. Pressure cooker was used for antigen retrieval, Of the cholangiocarcinomas, 85.7% (24/28) overexpressed p53. The intensity of staining in these cases varied from If in 2, 2+ in 10 and 3+ in 12 cases. None of the 28 tumours expressed bcl-2. The well differentiated nature of the tumour made assessment of dysplasia difficult, however, where present it did not express p53 or bcl-2, The bile duct epithelium adjacent to the tumour and in the control cases did not show any significant nuclear staining for either antigen. Conclusions: Overexpression of p53 appears to play an important role as a late event in the pathogenesis of cholangiocarcinomas, while we found no evidence of bcl-2 overexpression. The expression of p53 in 86% of the invasive tumours, as compared to its lack in the adjacent normal bile duct epithelium, makes it potentially useful in the diagnostic histopathology of these cases.