Several lines of evidence point to the involvement of the proto-oncogene c-raf-1 in the development of lymphoma and leukemia and in a previous study we found variants of this gene in 3 lymphoma patients. To see whether variation at this locus plays a role in predisposition to these cancers, we have examined the frequency of an unusual EcoRI allele of c-raf-1 in 99 non-Hodgkin's lymphoma and 28 acute lymphoblastic leukemia patients, and in 182 controls. To optimize the chance of detecting a difference, we selected 113 of the controls from geriatric patients with no family history of cancer. No difference in the frequency of the allele was found between patients and controls, thereby refuting our hypothesis that this polymorphism of the c-raf-1 locus contributes to genetic susceptibility to these two related cancers. We estimate that the frequency of the rarer b EcoRI allele of this locus is 0.091 +/- 0.012 in the Australian Caucasian population.