To examine the role of the type 1A (AT_1A) angiotensin receptor in renal growth and development, we analyzed F2 progeny from a series of crosses between F1 mice that were heterozygous for a targeted disruption of the AT_1Areceptor gene [Agtr1A-(+/−)]. Among 21-day-old weanling F2 mice, we found that 194 (32%) were homozygous for the wild-type alleleAgtr1A-(+/+), 299 (49%) wereAgtr1A-(+/−), and 119 (19%) were Agtr1A-(−/−). This differed significantly from the proportions predicted by Mendelian genetics (P = 0.01), suggesting that the complete absence of AT_1Areceptors is associated with a mild survival disadvantage.Agtr1A-(−/−) mice grew normally, and we found no significant differences in body weight or heart and kidney weights inAgtr1A-(+/+) andAgtr1A-(−/−) mice examined at 21, 60, and 100 days. Protein and DNA content of kidneys and hearts were also similar in weanling or adultAgtr1A-(+/+) andAgtr1A-(−/−) mice. By light microscopy with immunohistochemistry, kidneys fromAgtr1A-(−/−) were essentially normal, with two exceptions:1) there was marked hypertrophy of the juxtaglomerular apparatus (JGA) and proximal expansion of renin-producing cells along the afferent arterioles, and2) some glomeruli showed evidence of mesangial expansion. We did not find the severe renal vascular lesions or papillary atrophy that have been observed in angiotensinogen- or angiotensin converting enzyme-deficient animals. We conclude that the AT_1A receptor is not essential for the normal organogenesis of the kidney; however, its absence is associated with mild mesangial expansion and JGA hypertrophy.