In vitro isometric small vessel myograph experiments and pathological investigations were performed on rat middle cerebral arteries. Thirty-four animals provided 68 normal vessels, six further rats had the endothelial layer mechanically removed from their 12 arteries. Eighteen animals received gamma knife irradiation to the middle cerebral arteries. Fifteen of these received 50 Gray, and three 25 Gray dose to the 50% isodose and the contralateral vessels offered 20 Gray and 15 Gray irradiated specimens. Survival times varied from 12 weeks to 18 months. In the acute stage, abolition of potassium-induced relaxation occurred as early as 24 h after irradiation whilst in one year this reaction seemed to recover and remained active to 18 months. The contraction response to prostaglandin F2 alpha was diminished at six weeks in the 50 Gray-irradiated vessels. However, from one year further reduction was seen and by 18 months this response was totally abolished. We demonstrated reduction of contractile capability of the irradiated normal vessels while the vessels remained patent. When using low irradiation dose there were no pathological changes even at 18 months, but marked physiological changes could be demonstrated. Different vessel wall functions appear to have different radiosensitivity, time course and capability for regeneration.