The effects of oral aspirin (650 mg at 18 and 2 hours before testing) on the response to 10 minute venous occlusion in normal young adults (8 men, 4 women) was examined by fibrinolytic methods (euglobulin lysis, and radiofibrin assay of whole blood and plasma activities) and immunoassay of plasma tissue-type plasminogen activator (tPA). Aspirin had no effect on resting (pre-occlusion) values for any of these. Resting plasma tPA levels were approximately 3-fold greater in men than in women, with or without aspirin. Both before and after aspirin, occlusion increased euglobulin lysis activity, plasma fibrinolytic activity, and plasma tPA levels. In addition, there was an occlusion-related increase in cellular phase activity, determined by radiofibrin assay, which was similar, with and without aspirin, to the increase in plasma activity, indicating the participation of blood cells in the response to occlusion. Mean whole blood activity and cellular phase activity (whole blood less plasma activity) were increased 1.8- and 1.5-fold, respectively, by venous occlusion. In all subjects, the net effect of aspirin on occlusion-related increments in fibrinolytic activity were decreases in whole blood and cellular phase responses (p less than 0.05), without significant effects on plasma or euglobulin lysis activity. In contrast, aspirin treatment resulted in a 32% increase in mean individual increments in plasma tPA concentration with occlusion, an effect predominant in men. Aspirin interferes with the cellular phase fibrinolytic response to venous occlusion, and results in increased, rather than decreased, mean occlusion-induced increments in levels of plasma tissue activator, determined immunochemically.