The pattern of acquired mutations in the p53 gene can be used to study differences in factors contributing to carcinogenesis. We investigated mutations in exons 5-9 and adjacent intronic regions in 47 breast cancers of black women from Michigan, a population with the highest breast-cancer mortality in the US. The 16 mutations detected differed from those of other populations. In particular, the black women had an excess of A:T-->G:C transitions compared with rural white US midwest women. While the causes of the different pattern of acquired mutation remain to be determined, this molecular epidemiological approach detects the consequences of mutagenic processes in specific populations. Mutation patterns will constrain hypotheses to mechanisms consistent with the observed biochemical alterations.