Arteries denuded by the passage of a balloon catheter demonstrate marked smooth muscle cell (SMC) proliferation, whereas arteries denuded by a fine wire do not. We examined the possibility that vessel distension in addition to endothelial loss accounted for the SMC proliferation in the balloon model. Segments of rat left carotid isolated by temporary ligatures were distended hydrostatically with tissue culture medium at 300 mm Hg pressure via an external carotid cannula. Animals received either continuous [3H]thymidine infusion (intraperitoneally, Alzet pump, Alz Corp., Palo Alza, California) for 14 days or pulsed with [3H]thymidine at 1, 2, 3, or 7 days, and SMC proliferation was assessed by autoradiography. Distended vessels demonstrated patchy denudation acutely and complete endothelial regeneration by 3 days. No SMC were present in the intima at later times. Nevertheless, cumulative SMC proliferation over 14 days was 21 +/- 3% (perfused but not distended control: 0.8 +/- 0.6%; partially de-endothelialized but not distended control: 0.3 +/- 0.1%). Pulse-labeling demonstrated a peak of SMC proliferation between 2 and 3 days after injury. These results suggest that acute distension can contribute to the induction of SMC proliferation after endothelial denudation.