We have evaluated whether the addition of either bradykinin or histamine favours the lymphatic absorption of human recombinant interferon-alpha 2 (IFN-alpha 2) administered by the subcutaneous route. Subcutaneous administration of IFN-alpha 2 with bradykinin enhances IFN absorption via both capillaries and lymphatics, so that either the plasma or lymph areas under the concentration curves (AUC) increase significantly up to 1751 +/- 483 and 1319 +/- 608 IU/ml/min respectively as compared to the respective AUC values (613 +/- 208 and 483 +/- 213 IU/ml/min) obtained after IFN injection in normal saline. Since the lymph AUC/plasma AUC ratios remain unaltered, there is no preferential lymphatic absorption of IFN-alpha 2 after bradykinin administration. Dual-label experiments, 125I-IFN-alpha 2 in saline and 131I-IFN-alpha in saline containing 200 micrograms histamine were injected subcutaneously into the left and into the right shank of the same animal, gave similar results. The kinetics of 125I and 131I acid-soluble radioactivity confirm that histamine favours both plasmatic and lymphatic absorption.