There is little information about whether alveolar capillaries are altered in emphysema. To examine this question, we used scanning electron microscopic morphometry of microvascular corrosion casts to evaluate capillary structure in a guinea pig model of cigarette smoke-induced emphysema. After 6 months, the mean airspace size in the smoke-exposed animals was 157 +/- 31 microns and 106 +/- 11 microns (p < 0.001) in the control (air-exposed) animals. Because previous results from our laboratory had shown differences in size and density between central and peripheral capillaries in normal guinea pigs, these two areas were sampled separately in the present study. Capillaries in the emphysematous animals were narrowed compared with those in the control animals in both the center (mean diameter, 7.51 +/- 1.95 versus 8.93 +/- 2.01 microns, p < 0.001) and periphery (mean diameter, 8.52 +/- 2.13 versus 10.15 +/- 2.16 microns, p < 0.001) of the lobule. Smoke-exposed animals had a decreased capillary density in both the center (0.73 +/- 0.06 versus 0.79 +/- 0.05, p < 0.001) and periphery (0.77 +/- 0.07 versus 0.84 +/- 0.04, p < 0.001) of the lobule. We conclude that cigarette smoke-induced emphysema is associated with a diffuse and relatively uniform narrowing of capillaries with loss of capillary density throughout the lung. These findings may reflect diffuse smoke-induced abnormalities in the alveolar wall matrix with stretching of capillaries over enlarged airspaces and may partially explain the alteration of ventilation perfusion distribution in cigarette smoke-induced emphysema.