RB-protein status as determined by immunohistochemical analysis was compared with loss of heterozygosity (LOH) at the RB locus in 68 primary transitional-cell carcinomas of the bladder. Absence of RB-protein expression was found in 15 of 17 tumors in which LOH at the RB locus was identified, whereas 31 of 36 tumors from informative patients which showed no LOH had a normal RB-protein pattern (p < 0.001). Altered RB-protein expression was also more frequently seen in muscle-invasive and high-grade tumors (p < 0.003 and < 0.005, respectively). Our results indicate that LOH at the RB locus is highly correlated with loss of RB-protein expression in primary bladder carcinomas and further strengthens the notion that loss of RB function may be associated with more aggressive bladder tumors.