Although a practical and effective form of thrombolytic therapy has not yet been established, progress continues in achieving this objective. Current interest centers about urokinase, a promising thrombolytic agent obtained from human urine. Since a major clinical trial to evaluate urokinase in the treatment of acute pulmonary embolism is scheduled to begin shortly, this article describes the agent's development. The latter, requiring the close cooperation of the scientific community, the pharmaceutical industry, and the National Heart Institute, has resulted in [1] production of preparations suitable for clinical investigation; [2] evidence that the intravenous administration of the agent produces a reasonably predictable, reproducible, and sustained thrombolytic state in man; [3] demonstration that urokinase-induced states of accelerated thrombolytic activity are capable of inciting the lysis of thrombi; and [4] accomplishment of thrombolysis with minimal toxicity except that, on occasion, the thearpy is complicated by excessive bleeding induced by the intense thrombolytic state.