During cardiac surgery, the heart is infused with cold crystalloid cardioplegic solutions such as St. Thomas' Hospital (StT) solution, which contains high concentrations of K+ and Mg2+. The high K+ and Mg2+ block impulse conduction and inhibit Ca2+ influx, thereby arresting the heart and reducing cardiac oxygen consumption. Nevertheless, myocardial edema and post-operative abnormalities have been noted after cardioplegia and attributed to ischemia and reflow or to hypothermia. We found, however, that cold StT (9 degrees C) was hypotonic and induced cell swelling in the absence of ischemic injury. Cell swelling in cold StT was not due to hypothermia alone, but rather was caused by KCl influx and was prevented by partially replacing Cl- with an impermeant anion. After exposure to cold StT, cells transiently shrank to less than control volume on rewarming in physiological saline (Tyrode's solution, 37 degrees C). The transient shrinkage was blocked by ouabain suggesting that Na+ loading of depolarized hypothermic cells and Na(+)-K+ pump activation on rewarming were responsible. Hypothermic ventricular cells seem to follow Donnan equilibrium, and the product of [K+] x [Cl-] in cardioplegic solutions affects cell volume in the absence of ischemic injury.