We studied the effect of intravenously administered polyethylene glycol-conjugated superoxide dismutase (8,000 units/kg) on brain superoxide dismutase activity in 44 1-2-week-old piglets in the absence and presence of global cerebral ischemia and reperfusion. Four groups (n = 6 each) of piglets not exposed to ischemia were studied. Enzyme administration increased plasma superoxide dismutase activity from less than 5 to 142 +/- 8 units/ml (mean +/- SEM) without increasing brain activity (e.g., activities in the caudate were 7.9 +/- 0.5 and 8.1 +/- 0.4 units/mg protein) for up to 2 hours following administration. Four additional groups (n = 5 each) of piglets were given either enzyme or polyethylene glycol 5 minutes prior to 10 minutes of global cerebral ischemia induced by aortic cross-clamping followed by either 5 or 45 minutes of reperfusion. Enzyme administration increased plasma superoxide dismutase activity from less than 5 to 144 +/- 5 units/ml but failed to increase brain activity even after 45 minutes of reperfusion (e.g., activities in the caudate were 8.5 +/- 0.3 and 8.6 +/- 0.6 units/mg protein). We conclude that intravenous polyethylene glycol-conjugated superoxide dismutase does not increase superoxide dismutase activity in the brain despite global ischemia and reperfusion.