Restriction fragment length polymorphisms (RFLPs) of 2 oncogenes, c-Ha-ras and L-myc, have been analyzed in 101 patients with bone and soft-tissue sarcoma and in 98 normal individuals. The c-Ha-ras gene was highly polymorphic both in sarcoma patients and in normal individuals. In contrast to our previous observation in breast cancer patients (Honda et al., 1988), no significant difference in allele frequencies between normal and sarcoma populations was observed. The L-myc locus revealed 2-allele polymorphism, allele L (10-kb) and S (6.6-kb), after digestion with Eco RI. The allele frequencies of L and S in sarcoma patients were 0.381 and 0.619, respectively, and those in normal individuals were 0.485 and 0.515, respectively. While the distributions of alleles in both populations fitted well with the Hardy-Weinberg equilibrium, the frequency of the S allele was significantly higher in sarcoma patients than in normal individuals (p less than 0.05). When sarcoma patients were divided into male and female subpopulations, this difference was highly significant only in males (p less than 0.01) but not in females. Our results suggest that males carrying the S allele may be prone to develop sarcoma.