We sought to determine if multiple forms of mRNA for the angiotensin type-1 (AT1) receptor could be detected in rat kidney using the polymerase chain reaction (PCR) procedure. Amplification of rat kidney cDNA with oligonucleotide primers derived from the second and sixth transmembrane domains of the rat AT1 receptor yielded a single cDNA fragment 528bp in size. Sequence analysis indicated, however, that the cDNA fragment was a mixture of two highly similar gene products: the first cDNA was identical to the previously cloned AT1 receptor (termed here AT1A) whereas the second cDNA (termed here AT1B) was 92% identical at the nucleotide level and 96% identical at the amino acid level. Nucleotide substitutions were dispersed throughout the cDNA and 80% (33 of 41) were conservative. Significant levels of AT1A and AT1B mRNA were detected by PCR amplification of kidney poly(A)+ RNA and restriction enzyme analysis. These results indicate that at least two distinct AT1 receptor genes are expressed in rat kidney.