The effects of intrathrombic and intravenous injection of prostaglandin E1 (PGE1) during pulse-spray thrombolysis were studied in a rabbit model. Thrombi were produced in the inferior vena cava of 46 rabbits by means of vessel wall injury and placement of steel coils. At 2 days, pulse-spray thrombolysis was performed by using a catheter with multiple side holes spanning the clot. A control group received injections of saline. In all other rabbits, 3 mg of tissue-type plasminogen activator (tPA) was injected into the thrombus over 1 hour, and 500 U of heparin was intravenously administered. PGE1 was administered either intravenously (50 micrograms) or directly into the thrombus (10, 25, or 50 micrograms) in four groups. After treatment, the rabbits were killed and the residual clot was weighed. The relationship between clot length and volume measured on angiograms and clot weight was assessed in 13 additional untreated rabbits. Linear regression analysis was used to estimate the initial clot weight on the basis of measured clot length in treated animals. The extent of clot lysis was significantly greater with injection of tPA and 10-, 25-, or 50-micrograms PGE1 directly into the thrombous than with administration of tPA alone.