Alterations of the retinoblastoma (Rb) tumor suppressor gene and its encoded protein have been detected in a variety of malignant neoplasms. The authors have evaluated a series of 26 clinically localized stage B prostate adenocarcinomas for loss of heterozygosity (LOH) at 13q14 (including the Rb locus), rearrangements or partial deletions of the Rb gene, and alterations of Rb protein level by quantitative immunohistochemistry. LOH at the Rb locus occurred in 35% of the informative specimens. Of the specimens that showed LOH, 33% also had decreased or absent Rb protein in tumor cells by quantitative immunohistochemistry. In contrast, none of the specimens without LOH showed loss of Rb protein. Thus, LOH is correlated with loss of Rb protein. The authors conclude that alterations of the Rb tumor suppressor gene occur in a significant fraction of stage B prostate adenocarcinomas.