Compensated cardiac hypertrophy is associated with alterations in excitation-contraction (E-C) coupling. The resulting phenotype often includes enhanced Ca²⁺ transients and contraction. The present study investigated the progression of compensated hypertrophy by examining changes in Ca²⁺ flux pathways in 20 and 32 week (5 and 8 month) spontaneously hypertensive (SHR) and normotensive (WKY) rats. Rats were humanely killed and left ventricular myocytes were isolated using a standard enzymatic dispersion technique and loaded with fura-2 to monitor intracellular Ca²⁺. Cells were superfused with a physiological salt solution and Ca²⁺ transients elicited by field stimulation at 1 Hz. Data are presented as mean ± SEM and were analysed using two-way ANOVA, with significance assumed at 5%. Cell morphology was consistent with cellular hypertrophy in the SHR at 5 and 8 months of age (Table 1). Following steady-state stimulation, the Ca²⁺ content of the sarcoplasmic reticulum (SR) was assessed from the amplitude of the Ca²⁺ transient evoked by rapid application of 20 mM caffeine; Ca²⁺ transient amplitude and SR Ca²⁺ content were not significantly different in SHR myocytes at 5 and 8 months. The rate constant of decay (k) of the caffeine-evoked Ca²⁺ transient was examined in the absence and presence of Ni²⁺ to inhibit sodium calcium exchange (NCX). The component of Ca²⁺ decline attributable to SR Ca²⁺ uptake (i.e. k of the caffeine-evoked transient – k of the electrically-evoked Ca²⁺ transient) was not significantly affected by either strain or age. The Ni²⁺-sensitive rate constant was also unaffected by strain, but was significantly increased by age (5 vs. 8 months (k, s^-1) WKY: 0.13 ± 0.01 vs. 0.22 ± 0.02, n=16/28, P<0.05. SHR: 0.11 ± 0.02 vs. 0.19 ± 0.02, n=18/18, P<0.05). Calculation of relative activities from these rate constants showed a significant increase in the proportion of Ca²⁺ flux that occurred via NCX in the older animals, and an associated decrease in the proportion of Ca²⁺ taken up by the SR during the decay of the Ca²⁺ transient (P<0.05); these changes appear to be unaffected by hypertrophy.