Loss-of-heterozygosity (LOH) has been studied on 3p (von Hippel-Lindau gene locus), 5q and 17p (p53 gene locus) by a polymerase chain reaction (PCR)-based strategy in 42 sporadic renal cell carcinomas (RCC). LOH at seven microsatellite loci on 5q was investigated because a tumor suppressor gene on 5q involved in the development and/or progression of RCC has not yet been identified. LOH was found in seven (17%) RCC at single or multiple loci on 5q, 38% (11/29 informative cases) on 3p, and 6% (2/35 informative cases) on 17p. Replication error (RER) was present in 10% (4/42) RCC at single or multiple loci. The minimum region of deletion on 5q to account for LOH was mapped to 5q31.1 (interferon regulatory factor-1; IRF-1 locus), where LOH was detected in 23% (6/26 informative cases). LOH on 3p and 5q occurred in both stage 2 and more advanced (stage 3 and 4) tumors at similar incidences (41 and 33% on 3p; and 24 and 22% on 5q, respectively), suggesting that LOH on these chromosomes is an early genetic event. All RCC exhibiting LOH on 3p or 5q (IRF-1 locus) were the clear cell or the mixed clear and granular cell types. These findings suggest that LOH on 3p and 5q plays an important role in the genesis of clear cell RCC. In addition, only one tumor exhibited LOH on both 3p and 5q, which suggests that LOH occurs not sequentially but independently.