Antibodies raised to pure canine renal renin were used to probe homology of renin from other species. Goat, rabbit, and mouse antibodies exhibited similar properties and were specific for renin as confirmed by immunodiffusion, immunoelectrophoresis, and selective inhibition of renin enzymatic activity. Goat antibody also inhibited the enzymatic activities of rat, rabbit, hog, and bovine renin. Immunologic cross reactivity was further confirmed by direct binding and competition assays. Goat anti-(canine renin) antibody did not inhibit human or mouse renin activity, but readily bound to these enzymes, suggesting the presence of epitopes distant from the enzymatic site. Purified goat Fab retained only 10% to 20% of the anticatalytic activity of antibody, but this activity was largely recovered when donkey anti-goat antibody was added to the Fab-renin mixture. Thus, the major fraction (80% to 90%) of goat antibody exerted its anticatalytic activity by immune complex formation or steric hindrance and is not catalytic-site directed, whereas 10% to 20% binds an epitope at or near the catalytic site. (Hypertension 4: 341–347, 1982)