We used an isolated, pressurized, and perfused feline middle cerebral artery preparation to measure how changes in intraluminal pressure and alterations in O2 and CO2 affect vessel diameter and myogenic contractile activation before and after treatment with indomethacin (IND). Vessel diameters were measured over the pressure range 60-140 mm Hg. The arteries were then exposed to low O2 (50 torr) and/or high CO2 (65 torr) and diameters remeasured over the same range. Under control conditions, the arteries exhibited myogenic contractile activation. Exposure to low O2, high CO2, or a mixture of low O2/high CO2, increased vessel diameter but did not change the vessels' myogenic contractile responsiveness to changes in pressure. Arteries exposed to IND decreased in diameter but retained myogenic contractile activity. In the presence of IND, vessels dilated to both low O2 and a mixture of low O2/high CO2, but did not dilate to high CO2 alone. Under all conditions, vessels retained myogenic contractile activity. Results obtained under control conditions and low O2 confirm those of others using similar systems. Myogenic contractile activity in the presence of high CO2 or a mixture of low O2/high CO2 has not been previously reported. The dilation to low O2 but not to high CO2 in the presence of IND suggests that this drug's effects in cerebral arteries are not limited solely to inhibition of prostaglandin synthesis.