To evaluate the potential effect of heat stress in inhibiting neointimal hyperplasia after angioplasty in an experimental model.In vitro, proliferation and migration of heat-stress-induced and noninduced cells were compared with use of an endothelial cell/smooth muscle cell coculture model (five culture dishes in each experiment). Mild heat stress was induced via exposure of cultures to a temperature of 42 degrees C for 2 hours. In vivo, the neointimal thickness of ear arteries of Japanese white rabbits 7 days after denudation of endothelium was histologically evaluated in the control and heat-stress-induced groups (three rabbits in each group).Proliferation of heat-stress-induced smooth muscle cells declined significantly compared with that of noninduced cells in single-culture and coculture models. The migration rates of neither endothelial cells nor smooth muscle cells were significantly affected by heat stress. In vivo, the mean neointimal thickness was 13.8 micro m +/- 8.0 in the control group and 3.9 micro m +/- 2.1 in the induced group (P <.05).Induction of mild heat stress has great potential to reduce neointimal hyperplasia after angioplasty because it inhibits smooth muscle cell proliferation without inhibiting endothelial migration in vitro and suppresses neointimal growth in vivo.