In a previous study, the strength of the interaction between the nuclear stress proteins (sps) 25a, 70i, 72c, and 90 and the tumor suppressor protein p53 was determined by an in vitro fluorescence binding assay. The relative binding of the individual sps with p53, derived from the bone marrow of transgenic mice heterozygous at the p53 locus (p53+/-), was reduced compared to the interaction of sps and p53 derived from wild-type (p53+/-) mice. In order to determine if the genotype of the p53 donor or the genotype of the sp donor determined the binding efficiency, p53 expression was induced by retinoic acid and sp synthesis by bleomycin. P53 derived from either wildtype or heterozygous animals was cross-reacted with nuclear sps obtained from either wild-type or heterozygous animals. Each of the sps, 25a, 70i, 72c, and 90, bound to wild-type p53 with a similar efficiency, irrespective of the genotype of the sp donor mouse @53+/+ or p53+/-). In contrast, when the sp interaction with p53 obtained from the heterozygous mouse was measured, the relative value of the fluorescence complex was significantly reduced. The data suggest that the strength of the interaction between p53 and nuclear sps is related to the genotype of the p53 donor, and not to the genotype of the animals from which the sps are derived.