Recent studies have demonstrated that 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 (Kidney Int. 56: 509, 1999). Conversely, gestational high salt suppresses the fetal renin-angiotensin system (RAS) and provokes aberrant renal development in bradykinin B2-KO mice (Physiol. Genomics 3: 121, 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. Northern blot analysis revealed that renal renin mRNA levels are 50% lower in newborn B2-KO than wild type (WT) mice. Also, the age-related decline (birth to 60 days) in renin mRNA is greater in B2-KO than WT mice (3.5- vs. 2-fold, p<0.05). Renal angiotensinogen (Ao) protein levels, measured by Western blot analysis, are 3-fold higher in newborn B2-KO than WT mice (p=0.02). However, Ao mRNA levels were not increased in B2-KO suggesting that the higher Ao protein levels resulted from decreased renin-mediated cleavage of Ao. Significant, albeit similar age-related increases (8-fold) in angiotensin I-converting enzyme (ACE) activity are observed in B2-KO and WT mice. Renal AT1 receptor protein levels are not different in B2-KO and WT mice of either age group. Renal kallikrein mRNA levels and enzymatic activity increased significantly during postnatal maturation in both B2-KO and WT mice. However, the developmental increases in kallikrein are more pronounced in B2-KO compared to WT mice (mRNA: 8- vs. 3-fold; activity: 13- vs. 6-fold, p<0.05). We conclude that: 1) Bradykinin, either directly or indirectly, stimulates renin gene expression in the developing kidney. 2) Renal kallikrein is regulated via a negative feedback loop involving the B2 receptor, and 3) Renal Ao, ACE and AT1 are not bradykinin-target genes.