We searched for possible mutations in the E2F-binding region of retinoblastoma gene in primary human renal cell carcinomas, using polymerase chain reaction and single-strand conformational polymorphism analysis of RNA. Retinoblastoma gene mutation was detected in 1 of 21 cases (5%). DNA sequencing of the polymerase chain reaction product verified that this case had a 6-base deletion at the beginning of exon 8. Our findings suggest that mutation of the retinoblastoma gene is involved in only a subgroup of sporadic human renal cell carcinomas.