Intravesical Bacillus Calmette-Guerin (BCG) immunotherapy is currently the optimal choice for aggressive superficial bladder cancer, with a 70% response rate. This study investigated whether the antitumour response elicited by BCG could be improved by the addition of recombinant interferon alpha (IFN alpha) in the subcutaneous murine MB49 bladder tumour model. The combination of BCG and IFN alpha had superior and earlier antitumour activity than BCG alone for MB49 cells in culture. A total of 14/15 BCG plus interferon-treated mice and 8/16 BCG-treated mice became tumour free after treatment. BCG or the combination treatment significantly raised the T-helper 1 (Th1) cytokine IFN gamma levels compared with levels in all other groups. Whilst BCG therapy alone increased CD4+ and CD8+ populations in spleens, the combination of BCG and IFN alpha also increased alpha beta+ T cells significantly. Our results suggest that the combination of BCG and IFN alpha may represent a more efficacious therapeutic than BCG alone for superficial bladder cancer.