First published July 12, 2001; 10.1152/ajprenal.0020.2001.Angiotensin II type 1 (AT₁) receptor knockout (KO) mice exhibit an activated kallikrein-kinin system (KKS) that serves to attenuate the severity of the renal vascular phenotype in these mice (Tsuchida S, Miyazaki Y, Matsusaka T, Hunley TE, Inagami T, Fogo A, and Ichikawa I, Kidney Int 56: 509-516, 1999). Conversely, gestational high salt suppresses the fetal renin-angiotensin system (RAS) and provokes aberrant renal development in bradykinin B₂-KO mice (El-Dahr SS, Harrison-Bernard LM, Dipp S, Yosipiv IV, and Meleg-Smith S, Physiol Genomics 3: 121-131, 2000). Thus the cross talk between the RAS and KKS may be critical for normal renal maturation. To further define the developmental interactions between the KKS and RAS, we examined the consequences of B₂ receptor gene ablation on the expression of RAS components. Renal renin mRNA levels are 50% lower in newborn B₂-KO than wild-type (WT) mice. Also, the age-related decline in renin mRNA is greater in B₂-KO than WT mice (3.5- vs. 2-fold, P < 0.05). Although renal angiotensinogen (Ao) protein levels are higher in newborn B₂-KO than WT mice, Ao mRNA levels are not, suggesting accumulation of Ao as a result of decreased renin-mediated cleavage. Similar age-related increases (8-fold) in angiotensin I-converting enzyme (ACE) activity are observed in B₂-KO and WT mice. Renal AT₁ protein levels are not different in B₂-KO and WT mice. Furthermore, the developmental increases in renal kallikrein mRNA and enzymatic activity are more pronounced in B₂-KO compared with WT mice (mRNA: 8- vs. 3-fold; activity: 13- vs. 6-fold, P < 0.05). We conclude that 1) bradykinin stimulates renin gene expression, 2) renal kallikrein is regulated via a negative feedback loop involving the B₂ receptor, and 3) Ao, ACE, and AT₁ are not bradykinin-target genes.