We have studied the inhibition of both human and hog renins by compound 1 [Boc-Pro-Phe-N alpha-MeHis-Leu psi(CHOHCH2)Val-Ile-(aminomethyl)pyridine] using kinetics. The inhibition of human renin was shown to be time dependent and followed a minimal two-step mechanism. A loosely bound EI complex was formed rapidly with a dissociation constant, KI, of 12 nM. A second EI complex was slowly formed and was found to be 64-fold more strongly bound with an overall KI of 0.19 nM. The inhibition of human renin was shown to be competitive by both initial and final steady-state velocities. Compound 1 was also shown to be a competitive inhibitor of hog renin with a KI of 12 nM, but no evidence for time-dependent inhibition was detected. The differences in overall KI and inhibition kinetics may be a consequence of the similarities in structure between 1 and human angiotensinogen.