The response of the fibrinolytic system to hypophysectomy in the rat was studied. 4 and 6 weeks after hypophysectomy the tissue plasminogen activator activity (PAA) was significantly increased in the intima of the aorta, slightly but significantly increased in the renal medulla, and significantly decreased in the vessels of the testis. No change in the PAA of the caudal vena cava, heart, lung and renal cortex was noted. Also, the tissue plasmin inhibition remained unchanged. No effect on the PAA in plasma euglobulin fractions was observed, whereas F VIII was slightly but not significantly decreased 6 weeks after hypophysectomy.