Cytosolic free calcium (Caf) was measured in isolated renal cortical tubules from spontaneously hypertensive rats (SHR) and age-matched control Wistar-Kyoto (WKY) rats to evaluate whether the onset of hypertension is associated with a change in Caf. At the same time, the cellular mechanism by which differences in Caf occur between these two strains of rats was examined. Caf was significantly lower in renal tubules from 4- to 5-wk (142 +/- 6 vs. 187 +/- 15 nM), 6- to 7-wk (138 +/- 15 vs. 187 +/- 8 nM), and 8- to 9-wk-old (161 +/- 5 vs. 216 +/- 9 nM) SHR compared with age-matched WKY. The lower Caf in SHR tubules was considered to be the result of either an increase in Ca efflux or a reduction in Ca permeability. To the extent that metabolic inhibitors increased Caf but did not alter the difference between SHR and WKY, a primary difference in Caf efflux was excluded. Conversely, when Ca permeability was altered, either with Ca ionophores or incubation in Ca-free medium, Caf changed in the appropriate direction and the difference between SHR and WKY was no longer apparent. These results demonstrate that 1) the previously reported increase in Caf in circulating cells is not a universal feature of hypertension and 2) the lower Caf in renal tubules from SHR appears to be related to a lower Ca permeability. Whether the differences in Caf between SHR and WKY is a permissive factor for the renal contribution to hypertension remains to be elucidated.