This study investigates cellular alterations after directional atherectomy vessel injury (DI) in an experimental model in 50 pigs. Two hundred arteries were excised at eight different times (2 hours to 21 days) after DI and were examined by electron microscopy and immunohistochemistry. The extent of injury varied with the number of repetitive passes of the atherectomy catheter. According to the extent of injury the vessel segments with DI were assigned to three groups: intima injury (group 1), media injury (group 2), and adventitia injury (group 3). A myoproliferative response was found in relation to DI depth, increasing from group 1 (ratio tissue hyperplasia/media: 0.3 +/- 0.2; p < 0.001) to group 2 (ratio tissue hyperplasia/media: 1 +/- 0.5) and group 3. Intense neutrophil infiltration occurred in groups 2 and 3 (peak 12 hours after DI) and was followed by the early occurrence of synthetic smooth-muscle cells (SMC; > 50% of all SMC present). Volume fraction of desmin and actin was transiently reduced in injured media and myoproliferative tissue (7d: 9% vs > 90% normal media). SMC proliferation started in groups 2 and 3 at 48 hours and peaked at 7 days (+500% vs normal media, p < 0.001). After DI was done, vascular response started immediately and depended on injury depth. A transient myoproliferative response resulted, correlating with the extent of vessel trauma.