The purpose of this study was to investigate the effects of expression of CA IX, a marker of hypoxia, on outcome in bladder cancer. Immunohistochemistry was used to examine expression of CA IX in archival tissues of patients included in various therapeutic trials for transitional cell carcinoma (TCC) of the bladder. Data were collected on 57 patients who first presented with either invasive or superficial bladder cancer. Median follow-up for the 19 alive patients was 110 months (range 12 months to 14 years and 7 months). Median survival was 48 months (95% CI 35-110 months). Median survivals based on CA IX expression were as follows: there was a non-significant trend towards shorter survival for tumour expressing CA IX weakly (median 45 vs. 70 months, p=0.21). The hazard ratio for this variable is 1.5 (95% CI 0.8-3.0). Significantly more superficial bladder cancers than invasive cancers strongly expressed CA IX (82% vs. 52%; p=0.03). For non-invasive bladder cancer (n=28), CA IX positive patients had a median survival of 111 months while the median has not yet been achieved for CA IX negative patients (p=0.9). For invasive bladder cancer (n=29), CA IX positive patients had a median survival of 18 months as compared to 26 months for CA IX negative patients (p=0.94). There was a trend towards longer survival for tumour expressing CA IX strongly. This is likely to be a reflection of the significantly higher rate of strong CA IX expression in non-invasive cancers influencing these survival data.