Angiogenin interacts with actin to form a complex, which like actin itself, can accelerate plasmin generation by tissue plasminogen activator (tPA). In contrast to actin, the angiogenin-actin complex does not inhibit plasmin activity. In the presence of the angiogenin-actin complex, the overall proteolytic activity of a mixture of plasminogen and tPA is 11-fold higher than in its absence and 6-fold higher than in the presence of actin alone. These results suggest that binding and displacement of cell surface actin by angiogenin might be involved in cell migration and tumor invasion, processes that depend on the proteolytic degradation of basement membrane and the extracellular matrix. Therefore, the activity of the angiogenin-actin complex reported here may have physiological and pathological significance in the process of angiogenin-induced angiogenesis.