Porcine hearts have relatively few native collateral vessels and lack the propensity to develop normal perfusion to the collateral-dependent myocardium. To examine microvascular responses in the collateral-dependent region, collateral vessels were stimulated in pigs by the Ameroid constrictor technique. After 4-7 wk, isolated microarterial vessels (90-170 microns ID) were studied in a pressurized (40 mmHg), no-flow state. Microvessels from noninstrumented pigs were used as controls for vascular studies. Although myocardium in the collateral-dependent region showed minimal evidence of infarction, percent systolic shortening was reduced at rest and after pacing compared with myocardium in the normally perfused region. Relaxations to the receptor-mediated endothelium-dependent agents ADP and bradykinin were impaired in collateral-dependent coronary microvessels. Relaxations to the calcium ionophore A23187, which acts through a non-receptor-mediated mechanism, were similar in control and Ameroid microvessels. Relaxations to the endothelium-independent agent sodium nitroprusside were markedly enhanced in microvessels from the collateral-dependent region compared with microvessels from control hearts. In conclusion, receptor-mediated endothelium-dependent relaxation is impaired and endothelium-independent relaxation to sodium nitroprusside is enhanced in microvessels from myocardium perfused by immature collateral vessels.