Several studies have found postischemic regional accumulation of calcium to be time-dependent and coincident with the progression of ischemic cell change. In the most vulnerable cells in the hippocampus one would therefore expect to find a primary and specific early uptake of calcium after ischemia. Autoradiograms of 45Ca and 3H-inulin distribution were investigated before and 1 h after 20 min ischemia in the rat hippocampus. Two different methodological approaches were used for administration of 45Ca: (a) administration via microdialysis probes, (b) intraventricular injection. During control conditions the 45Ca autoradiograms showed variations in distribution volume in accordance with 3H-inulin determination of extracellular space size. One hour after ischemia a massive accumulation of 45Ca was found in the dentate hilus. No change in the distribution pattern of 3H-inulin could be demonstrated 1 h after ischemia. We suggest that 45Ca accumulation in dentate hilus 1 h after ischemia is a result of increased Ca2+ uptake before irreversible cell damage occurs and is not due to passive influx of calcium across a leaky plasma membrane.