Effects of acute changes in osmolality and sodium concentration (Na) on myocardial contractility (MC) were examined in anesthetized dogs. Using a carotid to left anterior descending bypass, 4 cc of NaCl and/or dextrose of varying osmolality as injected and the percentage of change in MC measured. At Na = O mEq/L, a positive inotropic response occurred, which varied inversely as osmolality increased from 300 (MC = 100 +/- 23%) to 700 mOsm/L (MC = 39 +/- 10%, p less than 0.01). Similar ranges of positive responses of lesser magnitude were noted at Na = 75 mEq/L. At Na = 150, 190, or 350 mEq/L, similar increments in osmolality caused an increasingly negative inotropic response. An inverse relationship between Na and MC was noted with osmolality held constant. Injections of the nonionic contrast agent, P297, in 5% dextrose or 0.9% NaCl, resulted in 28 +/- 3% or -17 +/- 4% (p less than 0.01) change in MC, respectively. Sodium concentration and osmolality have independent effects on MC. Hyperosmolality/hypernatremia causes a negative inotropic response while hyponatremia causes a positive one.