The influence of hypoxia and acidosis on the release of vascular plasminogen activator was studied in the isolated perfused pig ear. Perfusion with deoxygenated or acid solutions led to significant increases in plasminogen activator release (p less than 0.001); acid solutions of pH 6.7 were more effective than those of pH 6.9. Perfusions with lactate and AMP, two metabolic products which might act as mediators of fibrinolytic stimulation during hypoxia, resulted in moderate increases of plasminogen activator in the effluent (p less than 0.01).