Intratumor heterogeneity is a major problem in immunodiagnosis and treatment of carcinomas. To elucidate the well-known heterogeneity in transitional-cell carcinomas of the ability to express blood group ABO isoantigens, a stereological estimate of the mean nuclear volume in areas expressing blood group antigens was compared to the estimate from areas of identical pathological grade at which antigen expression was deleted. Four microscopic fields were examined from antigen-positive and four from antigen-negative areas in sections from 21 blood group O and 20 blood group A individuals. The sections were stained before examination by an indirect peroxidase method using monoclonal anti-H and anti-A antibodies. The mean nuclear volume increased, as expected, with increasing pathological grade. In blood group O individuals the mean nuclear volume was 241.5 microns 3 in antigen-positive areas and 338.2 microns 3 in antigen-negative areas (2p less than 0.0005) of identical pathological grade. In group A individuals the mean nuclear volume was 217.1 microns 3 in positive areas and 351.1 microns 3 in corresponding negative areas (2p less than 0.0025). The variation in volume parameter was essentially caused by a true variation between tumors (greater than 82%). The results indicate a complex biological mechanism associated with the cellular ability to express blood group antigens.