Secretory leukoprotease inhibitor (SLPI) comprises two homologous domains: the C-terminal domain contains the reactive site, while the function of the N-terminal domain remains unknown. In order to elucidate the function of the N-terminal domain, we studied the kinetics of reactions of human leukocyte elastase with two recombinant forms of SLPI: the full-length inhibitor and the C-terminal domain alone. The reactions of elastase with the full-length inhibitor and the C-terminal domain share the same association rate constant, 2 x 10(6) M-1 s-1, but the complex formed with the C-terminal domain is less stable, with a dissociation rate constant of 8 x 10(-4) s-1, 5 times higher than that of the complex with the full-length inhibitor. The binding of the full-length inhibitor to elastase is greatly accelerated by polyanions. In the presence of submicromolar concentrations (1 microgram/mL) of heparin, the association rate constant is increased by more than 1 order of magnitude. The binding of the C-terminal domain alone to elastase shows much lower sensitivity to heparin; in the presence of 5 microM (25 micrograms/mL) heparin, association of the C-terminal domain with elastase reaches a maximum rate of 7 x 10(6) M-1 s-1, about 3 times higher than the rate in the absence of heparin. Similar differential effects of heparin have been observed on the reactions of alpha-chymotrypsin with the two recombinant forms of SLPI.2=