Physiological saline with or without substance P (50 ng/ml) was infused into the humeral artery in 6 healthy males. Indices of fibrinolytic activity (whole blood diluted lysis time, euglobulin lysis time, lysis areas in non-heated fibrin plates produced by plasma or euglobulin precipitate, plasminogen plasma levels, alpha 2-macroglobulin, C1-inhibitor, and alpha 2-antiplasmin) were evaluated in the homolateral antecubital vein before and after 5 min of substance P or saline infusion. After substance P the fibrinolytic activity increased, as can be seen from the shortening of lysis times (p < 0.01) and enlargement of the lysis areas (p < 0.01). A reduction of plasminogen plasma levels (p < 0.01), associated with a decrease in alpha 2-antiplasmin (p < 0.01), was also found. Alpha 2-macroglobulin and C1-inhibitor were instead unaltered by the peptide. The saline infusion, on the other hand, was unable to modify any of the examined indices. We concluded that exogenous substance P given intra-arterially increases fibrinolytic activity in locally-sampled venous blood through a mechanism which remains to be elucidated.