The middle cerebral artery (MCA) was irradiated in 94 rats using the Gamma Knife. The vessels receiving 20, 50, 80 and 200 Gy were removed 24 h later and mounted on a myograph. Contractility responses to potassium and prostaglandin (PG) F2 alpha were tested. After precontraction with PGF2 alpha, the relaxant effects of histamine, papaverine, L-arginine and sodium nitroprusside were examined. Other vessels were preincubated with ouabain or N omega-nitro-L-arginine methyl ester before testing with the relaxant agents. After irradiation, the contractile response to maximal potassium and PGF concentrations was diminished, suggesting dose-dependent radiation damage to the contractile mechanism. The normal MCA shows an initial relaxation in the presence of a low K+ concentration, which is Na+, K(+)-ATPase dependent. According to this study, the endothelium-derived relaxation function was suppressed by radiation, suggesting that there is an early change in irradiated vessels, demonstrable by functional studies, which affects both the smooth muscle and endothelial layers.