The purpose of this study was to clarify whether continuous infusion of recombinant tissue plasminogen activator (rtPA) prevents intimal hyperplasia at the site of arterial injury. Forty-three Kurosawa and Kusanagi hypercholesterolemic (KHC) rabbits which underwent balloon angioplasty of the right common iliac artery were randomly divided into 2 groups; rtPA for 7 days (n=29) and untreated (n=14). The former group was subdivided into a high-dose group (n=15) (2 mg/kg per day continuously for 7 days after 3 mg/kg for 4 h) and a low-dose group (n=14) (0.6 mg/kg per day for 7 days after 0.6 mg/kg for 4 h). Balloon angioplasty was performed with a 2.5-mm balloon (3×60-sec, 6-atm inflations at 60-sec intervals) 1 h after the initiation of rtPA infusion via an ear vein. The iliac arteries of the rabbits were histologically studied at 28 days. The cross-sectional areas of the intima, media, and adventitia were calculated at the site of intimal hyperplasia. The intimal cross-sectional area was 0.07±0.11 (mean±SD) mm² for the high-dose rtPA group and 0.11±0.07 mm² for the low-dose rtPA group, and both of these values were significantly less than that for the control group (0.57±0.21 mm² p<0.01). The ratio of the intimal to medial cross-sectional area was significantly (p<0.01) Iower for the rtPA groups than for the control group (high-dose rtPA; 0.10±0.13, Iow-dose rtPA; 0.21±0.19, control; 1.25±0.55). In conclusion, continuous infusion of rtPA for 7 days prevented intimal hyperplasia after balloon injury. (Jpn Circ J 1996; 60: 889 - 894)