We have evaluated whether the addition of either bradykinin or histamine favours the lymphatic absorption of human recombinant ¡nterferon-a2 (IFN-cq) administered by the subcutaneous route. Subcutaneous administration of IFN-a2 with bradykinin enhances IFN absorption via both capillaries and lymphatics, so that either the plasma or lymph areas under the concentration curves (ACJC) increase significantly up to 1751 ±483 and 1319±608 l(_l/ml/min respectively as compared to the respective ACJC values (613±208 and 483±213 ICJ/ml/min) obtained after IFN injection in normal saline. Since the lymph ACJC/plasma ACJC ratios remain unaltered, there is no preferential lymphatic absorption of IFN-a2 after bradykinin administration. Dual-label experiments, 125l-IFN-a2 in saline and 131l-IFN-a2 in saline containing 200 jig histamine were injected subcutaneously into the left and into the right shank of the same animal, gave similar results. The kinetics of 125l and 131l acid-soluble radioactivity confirm that histamine favours both plasmatic and lymphatic absorption.