Objectives: The aim was to investigate the effects of an exogenous source of nitric oxide on in vivo platelet adhesion at the site of endothelial denudation after balloon angioplasty. Methods: The study group consisted of 12 anaesthetised Large White pigs. Pigs were randomised to receive SIN-1 (3-morpholino-sydnonimine), an exogenous donor of nitric oxide, or placebo before and during balloon induced vessel wall injury. Platelet deposition was quantified using the injection of autologous indium-111 labelled platelets. Platelet function was also monitored by the measurement of bleeding time and ex vivo whole blood aggregometry. Results: Superficial vessel wall injury was confirmed histologically and platelet monolayer formation was demonstrated by scanning electron microscopy. Platelet deposition at the site of endothelial denudation was markedly reduced following SIN-1 administration compared to placebo: 1.266(SEM 0.063) v 1.732(0.060) log platelets x 10(5).cm-2, p=0.001. SIN-1 raised platelet cyclic GMP concentration, from 4.47(2.48) to 6.14(2.44) pg.platelet-1 (p<0.01) and prolonged the bleeding time, from 135(5) to 202(6) s (p=0.001), but had non-significant effects on ex vivo whole blood aggregometry. Conclusions: Exogenous nitric oxide, through the activation of platelet soluble guanylate cyclase, inhibits platelet adhesion in vivo following balloon angioplasty.