Whole cerebral and isolated mitochondrial calcium levels were determined in normal and chronically uremic Sprague-Dawley rats. Uremia was induced by a two-stage 5/6 nephrectomy 4 weeks prior to study. Serum was obtained for urea, calcium, magnesium, phosphate, and i-PTH. Mitochondria were isolated by gradient centrifugation and calcium was determined by flameless atomic absorption spectrophotometry. The results demonstrate that mitochondrial calcium levels in uremic rats are not different from normal (8.0 +/- 2.8 vs. 7.8 +/- 1.8 nmoles/mg protein) despite an 11% increase in whole cerebral calcium concentration (17.3 +/- 2.0 vs. 15.5 +/- 2.8 nmoles/mg protein; P less than 0.005) in 24 severely uremic rats (BUN greater than 18.0 mmoles/liter). Multiple regression analysis demonstrates a significant positive correlation between cerebral calcium concentrations and both serum calcium (P less than 0.005) and serum magnesium levels (P less than 0.005). No relationship was found for urea, serum phosphate, or i-PTH. Similar analysis of mitochondrial calcium concentration demonstrated a significant positive correlation with serum calcium (P less than 0.005) and i-PTH (P less than 0.05) suggesting that increased PTH may be necessary for maintaining normal intracellular calcium levels in uremia. We conclude that uremia in the rat is associated with a small rise in whole cerebral calcium but that intracellular calcium as reflected by mitochondrial levels is not elevated.