Studies on the active center of human plasmin indicate that it is functionally identical with those of bovine plasmin and bovine trypsin. Its similarities to and differences from bovine thrombin duplicate those previously demonstrated between the latter and both bovine plasmin and trypsin. The data suggest that the basic structural geometry and group function of an active center capable of catalyzing a successful enzymatic mechanism, in these studies the tryptic function, is maintained for the active centers of different tryptic enzymes both within a species and in evolutionary shifts from species to species.