It was recently reported that different rare alleles at the Ha-ras-1 locus occurred at a significantly higher combined frequency in cancer patients than in an unaffected population. In particular, melanoma patients were reported to have a significantly higher frequency of such alleles. We have examined the frequency of rare Ha-ras-1 alleles in a large number of cases of sporadic melanoma. Our results indicate that the distribution of rare alleles in this population does not differ from that found in normal populations. Also, to test the hypothesis that a hereditary predisposition to melanoma could be inherited via an allele at the Ha-ras-1 locus, we examined the transmission of the segment of the short arm of chromosome 11 (11p) carrying the Ha-ras-1 locus in a number of families previously shown to exhibit a hereditary predisposition to melanoma and its precursor lesion, the dysplastic nevus syndrome (DNS). Our genetic linkage results thus obtained strongly exclude the association of a predisposition to melanoma or the precursor lesion with the inheritance of the Ha-ras-1 locus or the segment of chromosome 11 on which it is located. These results imply that hereditary predisposition to melanoma is associated with genes other than the Ha-ras-1 locus, contradicting the original suggestion of Krontiris et al., made on the basis of either an inadequate sample size or other misleading experimental factors.