The extent of cholinergic-sympathetic interaction in the heart was examined in the resting control state and after isoproterenol stimulation in eight conscious dogs. Sonomicrometer crystals and solid-state pressure transducers were implanted in the left atrium and the left ventricle to evaluate mechanical function while heart rate was held constant by atrial pacing. Edrophonium (0.5 mg/kg i.v.) was given as a single dose at rest and during increased sympathetic tone produced by continuous infusion of isoproterenol (0.08 micrograms/kg/min). In the control state, edrophonium administration caused no change in left ventricular dP/dt, fractional shortening or velocity of contraction, but produced significant (P less than .001) decreases in left atrial fractional shortening and contraction velocity. During isoproterenol infusion there were significant increases in dP/dt, the velocity of contraction and fractional shortening in both left atrium and ventricle (P less than .001). Administration of edrophonium during this increase in inotropic state produced significant (P less than .01) decreases in left ventricular dP/dt, fractional shortening and contraction velocity. Moreover, after edrophonium, left atrial fractional shortening and velocity of contraction were decreased to values that were significantly (P less than .001) less than control. Thus, cholinergic stimulation caused selective depression of left atrial systolic function at rest and depression of both left atrial and ventricular function during sympathetic stimulation.