Summary1. The effect of a standard, potent fibrinolytic enzyme therapy has been compared in fasting and lipemic dogs.2. The standard fibrinolytic regimen resulted in the complete dissolution of all clots produced experimentally in the fasting state in 10 dogs.3. Clots formed during alimentary lipemia exhibited a markedly increased resistance to the standard fibrinolytic regimen in 6 dogs.4. An increase in anti plasmin fibrinolytic titer with concomitant decrease in spontaneous fibrinolytic activity was observed in 15 dogs following the administration of a fatty meal. No difference in fibrinolytic activity and APF titer was demonstrable in fasting and lipemic blood samples obtained during fibrinolytic enzyme treatment.5. The possibility of the presence of specific inhibitors against the fibrinolytic enzyme in clots formed during lipemia has been investigated and the evidence to support this theory is discussed.