Polyamines are intracellular cations that are thought to play a role in the regulation of cell growth and differentiation. This study was undertaken to determine if inhibition of ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine synthesis, suppresses formation of intimal hyperplasia (IH) after arterial injury. Twenty New Zealand white rabbits underwent balloon catheter deendothelialization of a common carotid artery. Treated animals (n = 10) were given alpha-difluoromethylornithine (DFMO), an inhibitor of ODC, ad lib in drinking water as a 2% solution. DFMO was begun 3 days prior to surgery and continued until vessel harvest. Vessels were perfusion-fixed at harvest, 2 (n = 10) and 4 (n = 10) weeks postoperatively. All arteries remained patent. There were no histologic differences in the IH between treated and untreated animals. The intima and media surface areas on serial arterial cross sections were determined using computer-assisted planimetry. There was a significant difference in the IH surface area of injured arteries between untreated and DFMO-treated animals at both 2 (17.6 +/- 2.0 vs 3.0 +/- 1.6 microns 2; P less than or equal to 0.001) and 4 weeks 27.4 +/- 5.6 vs 7.1 +/- 1.8 microns 2; P less than or equal to 0.008). No differences were seen in medial thickness. We conclude that ODC inhibition reduces early development of IH after arterial deendothelialization. These data support the hypothesis that polyamines may be cellular messengers involved in the regulation of IH formation.