Incidence of the loss of heterozygosity on chromosome 3p was evaluated using 7 polymorphic probes in 35 Japanese patients with sporadic renal cell carcinoma (RCC). Overall frequency of the loss of heterozygosity on 3p was 53%, representing 16 of 30 informative cases. Examination of the relationship between histopathological phenotypes of RCC and incidence of the 3p loss revealed that the loss of heterozygosity in clear cell type tumors (75%, 12 of 16) was significantly (P less than 0.01) more frequent than that in granular cell type tumors (14%, 1 of 7). In addition, three mixed cell type tumors, consisting predominantly of granular cell components, showed no loss of chromosome 3p loci. These findings may support the notion that the loss of heterozygosity on chromosome 3p is a nonrandom event in the tumorigenesis of sporadic RCC, and suggest that this type of chromosomal rearrangement is specific to the clear cell phenotype of RCC.