1 We studied DMP728, a non-peptide glycoprotein (GP) IIb/IIIa receptor antagonist, for prevention of coronary artery thrombosis or rethrombosis in a chronic canine model subjected to arterial injury. 2 In protocol I, DMP728 (1.0mg kg-', i.v., n = 8) or saline (n = 8) was administered and a 150 JA anodal current was applied to the intimal surface of the left circumflex coronary artery (LCX). Dogs were monitored for 6 h and again on each of 5 subsequent days. 3 Ex vivo platelet aggregation was inhibited but returned to baseline day after drug administration. Thrombus weight was reduced (saline, 20.7 ± 5.0 mg; DMP728 1.7 ± 0.4 mg; P < 0.05), as was infarct size [saline, 27.5 ± 4.3; DMP728, 1.6 ± 0.7 (per cent left ventricle); P<0.05]. All control animals died by day 3, while all but one of the treated dogs survived the entire protocol (P <0.05). 4 In protocol II, an LCX thrombus was induced and thrombolytic therapy was initiated 30 min later. DMP728 (1.0 mg kg-', i.v., n = 8) or saline (n = 8) was administered 5 min after recombinant tissue-type plasminogen activator infusion had begun. The incidence of reocclusion was reduced by DMP728 (saline, 4/8; DMP728, 1/8). One day after thrombolysis, 7/8 DMP728-treated animals were alive compared with 1/8 in the control group (P = 0.01). 5 DMP728 inhibited ex vivo platelet aggregation, prevented primary and secondary occlusive thrombus formation, reduced thrombus weight and infarct size and increased survival in a chronic canine model of coronary artery thrombus formation. DMP728 is an effective anti-platelet intervention when used as the singular adjunctive agent in association with thrombolytic therapy.