Local delivery of pharmacological agents into the vessel wall has been extensively studied to prevent restenosis after coronary angioplasty. Alcohol solution was found to affect cellular responses to growth stimulation. This study was carried out to examine the effect of local delivery of alcohol solution on intimal proliferation following balloon injury. New Zealand white rabbits of 2-3 kg underwent balloon denudation of bilateral iliac arteries. Following denudation, 2 ml 10% or 15% alcohol solution was infused into one iliac arterial wall using a Wolinsky porous balloon catheter. The other iliac artery of the same animal received local delivery of normal saline and was used as the control. The animals were killed at 2 weeks. The neointimal areas of alcohol treated vascular segments were significantly less than those of control segments in both 10% (n = 10) and 15% (n = 11) groups (65 +/- 16 versus 113 +/- 20 x 10(3) microns2 in 10% group, P < 0.0001; 48 +/- 15 versus 107 +/- 10 x 10(3) microns2 in 15% group, P = 0.002). In order to determine the effect of alcohol solution on smooth muscle cell proliferation, a method of quantifying phenotypic conversion of smooth muscle cells was chosen. This consists of a measurement of volume fraction of the synthetic organelles (VFSO) of vascular smooth muscle cell profiles (SMC) using transmission electron micrographs taken in the animals killed at day 8. The VFSO of SMC of the control sites were significantly greater than those of paired 10% alcohol treated arteries in both intima (0.39 +/- 0.02 versus 0.21 +/- 0.01, P < 0.0001) and media (0.33 +/- 0.03 versus 0.19 +/- 0.02, P < 0.0001). Similar findings were noted in the 15% alcohol treated group. It is concluded that intramural alcohol delivery using porous balloon catheter is effective in reducing neointimal proliferation in rabbit iliac arteries after balloon injury. The mechanisms of action may involve direct inhibition of cellular responses to growth stimulation.