The enhancement of canine arterial thrombolysis with native tissue type plasminogen activator (nt-PA) obtained from human-derived normal cells by pretreatment with heparin or the defibrinogenating agent, batroxobin, was evaluated with angioscopy. The nt-PA, 0.25 mg/kg, was infused intravenously to lyse 1-hour-old thrombus (eight thrombosed arteries without medication, seven with nt-PA alone, seven with nt-PA and heparin, and seven with nt-PA plus batroxobin). Angioscopy provided a cross-sectional view of the vessel lumen with clear visualization of the thrombus. Thirty minutes after nt-PA infusion, the percent luminal obstruction decreased from 74 to 61 in nt-PA alone (p less than .025), from 77 to 37 in nt-PA plus heparin (p less than .005), and from 79 to 25 in nt-PA plus batroxobin (p less than .005). Fifteen minutes after drug infusion, plasma fibrinogen levels decreased to 89% of preinfusion value in nt-PA alone, to 84% in nt-PA plus heparin, and to less than 5% in nt-PA plus batroxobin. Thus rapid infusion of nt-PA alone provided slight thrombolytic effects. However, heparin and batroxobin showed marked enhancement of thrombolytic effects of nt-PA.