To investigate the possible role of genomic aberrations of chromosome 9p21 in the tumorigenesis of human renal cell carcinoma (RCC), 40 sporadic RCCs were studied using PCR analyses. The tumours were predominantly low stage and low grade. Loss of heterozygosity (LOH) was observed in nine of 39 informative cases, but no homozygous deletion was noticed. Hypermethylation of the promoter region of p16 occurred in eight of the 40 RCCs. No correlation was found between hypermethylation of the p16 gene and LOH on 9p21. A similar level of LOH and methylation was observed in the 40 RCCS regardless of histology, grade and stage. These results suggest that inactivation of p16 and the possibility of other unknown tumour suppressor genes located on other chromosomes could be involved in the pathogenesis of RCC.