Polymeric fibrin is a strong enhancer of the activation of plasminogen by t-PA. At least two types of sites are involved in this enhancement i.e. a site within A alpha-(148-160), and a site within gamma-(311-379). These sites are not accessible in fibrinogen, but are exposed upon conversion of fibrinogen to fibrin. This explains why fibrinogen has no rate-enhancing properties, and helps to explain the effects of fibrin. Fibrin with its ordered structure appears to exert its rate-enhancing effect by presenting the above sites for interaction with t-PA and plasminogen; thus concentrating and correctly orienting these two reactants on its surface and inducing conformational changes which lead to higher catalytic efficiencies.