Cobalt-55 ((55)Co) has been shown to be an interesting positron emission tomography (PET) tracer that may reflect calcium (Ca) influx in damaged cerebral tissue. Because Ca load is important in the ischemic cascade, the exact meaning of (55)Co PET in stroke patients has to be shown. The present study compares the degree of (55)Co uptake to regional cerebral blood flow (rCBF) and regional cerebral metabolic rate for oxygen (rCMRO(2)) values in brains of patients with ischemic stroke. Eighteen patients with an ischemic event in the middle cerebral artery territory were examined with PET using, in the same session, (55)Co and the (15)O steady state technique. The (55)Co ratio was assessed in ischemic and infarcted regions and compared with the corresponding rCBF and rCMRO(2) values. The average (55)Co ratio is inversely correlated to the rCBF and rCMRO(2) values. Also (55)Co accumulation tends to increase during the weeks after the onset of stroke and decreases down to normal levels after 6 months. The degree of (55)Co uptake corresponds to the severity of the ischemic damage within the first month after stroke. As it increases with time, it probably reflects the Ca accumulation caused by the progression of the inflammatory response within and around the infarct core.