Transgenic mice were produced harboring the p53 murine cDNA clone regulated by the SV40 enhancer-promoter region 5' to the cDNA and the small t antigen splice sites, and poly(A) addition signals 3' to the cDNA. This construction was not expressed in these mice. The presence of several murine p53 introns in the cDNA, however, permitted expression of the transgene mRNA in several tissues of transgenic mice. The insertion of intron 4 led to the preferential expression of the transgene mRNA in spleen cells, where the endogenous p53 gene is also expressed at high levels. While intron 4 promoted high levels of p53 mRNA expression in a tissue-preferred manner in transgenic mice, there was no evidence that intron 4 could act as an enhancer of transcription in cell culture or in transgenic animals. The presence of some p53 introns appears to be critical for the regulation of this gene in vivo.