Patients with hyperlipoproteinaemia or spontaneous thromboembolism, known to be poor responders to DDAVP or to venous occlusion with regard to the rise in fibrinolytic activity of the blood, appeared to show a normal increase in t-PA-antigen after the same procedure. In their plasma a higher than normal level of free, fast-acting t-PA-inhibitor was found as measured by titration with purified t-PA. This free t-PA-inhibitor level only decreased after the test, in contrast to its complete disappearance in normal responders. The same happened in a healthy volunteer who failed to exhibit a rise in fibrinolytic activity after exhaustive exercise. We suppose that the lack of response of the fibrinolytic activity in these cases is due to a high inhibitor level and not to impaired release of t-PA into the blood. In contrast, patients with terminal renal insufficiency showed only a slight increase in t-PA-antigen after DDAVP. The level of free fast-acting inhibitor was normal in most cases and did not change appreciably during DDAVP-infusion. In these patients, a true impairment of the release of t-PA appears to exist.