To evaluate the importance of time, temperature, and cardioplegia on the ability of the canine myocardium to maintain functional and ultrastructural integrity following induced arrest, we studied 220 dogs by varying myocardial temperature (34 degrees, 24 degrees, and 11 degrees C.), arrest time (0 to 120 minutes), and cardioplegic agents. Change in left ventricular function (LVF) was defined as the arithmetic difference in the center of mass between prearrest and postarrest LVF curves and was expressed as percent recovery of left ventricular stroke work. Left ventricular biopsies were obtained for semiquantitative electron microscopic analysis. After 90 minutes of cross-clamping, only hearts protected with combined hypothermia (H) and potassium-induced cardioplegia (K) significantly recovered prearrest function (24 degrees C.--80 percent, 11 degrees C.--99 percent). Hypothermia (H) alone for 90 minutes was less protective (24 degrees C.--49 percent, 11 degrees C.--59 percent). H preserved 84 percent of function after 60 minutes and 91 percent after 45 minutes. Normothermic arrest resulted in only 39 percent return of function at 45 minutes but could be extended with potassium-induced cardioplegia(K) to 78 percent at 60 minutes and 54 percent at 90 minutes. The addition of procaine plus HK improved protection over HK alone (95 percent versus 80 percent) but by itself was not effective. Neither hydrocortisone nor pretreatment with glucose-insulin-potassium, branched chain amino acids, or propranolol increased the protective effect of HK plus procaine. Inadequately protected groups (normothermia or H without K) showed more myocytic and capillary endothelial damage than the HK groups. No technique of myocardial protection studied completely preserved LVF, but the combination of HK plus procaine resulted in maximal recovery of LVF following cross-clamping for up to 120 minutes.