We evaluated the use of simple balloon overinflation to induce neointimal hyperplasia in a porcine model of coronary artery restenosis. By using standard percutaneous transluminal coronary angioplasty techniques, left anterior descending (LAD) and/or left circumflex (LCX) coronary arteries of either juvenile feeder pigs or adult Yucatan minipigs were intentionally overinflated. Four weeks later, resultant neointimal hyperplastic responses (neointima/media area; NI/M) were quantitated morphometrically. At all ballooned sites neointimal hyperplasia occurred only when the internal elastic lamina (IEL) was ruptured; the degree of hyperplasia correlated directly with the injury index, that is, the percentage of IEL circumference that fractured (r = 0.74; n = 25; p < 0.05). Despite similar injury indexes in the LAD bed, there was a trend (p = 0.07; analysis of variance) toward greater NI/M ratios in the Yucatan minipig versus the feeder pig group (1.14 +/- 0.21 vs 0.73 +/- 0.09, n = 7/group). We found no such trend in the LCX bed, where the injury index (25.7% +/- 3.5%) was significantly greater than that of the LAD (18.2% +/- 1.2%, p < 0.05). If variations in balloon-induced vascular injury are accounted for, the technique of balloon overinflation of coronary arteries should prove useful in testing potential antirestenotic agents in either adult or juvenile pigs.