The effects of an extracellular sodium (Na) concentration of 200 mM on function, ionic exchange, and water movements were examined in the vascularly perfused rabbit intraventricular septum. When the perfusate was switched from 1.42 mM Na to 200 mM Na, dP/dt fell 20.4% over 2 minutes; dP/dt then recovered to the control level. The time course of the functional recovery correlated with the uptake of Na into the slowly exchangeable fraction of the tissue, and the rate of recovery in 200 mM Na depended on the frequency of contraction of the preparation. During perfusion with 200 mM Na, a 41% increase in slow-phase Na content compared with the content during perfusion with 142 mM Na was observed. The hyperosmolar perfusate induced a 21% cellular dehydration within 10 minutes as estimated from measurement of 10-minute35SO4space and total tissue water. The time course of dehydration was much more rapid than the time course of functional recovery. Calcium (Ca) influx during the period when dP/dt had returned to control levels in 200 mM Na was the same as it was during a control period in 1.42 mM Na. Thus, there appears to be a Na-Ca exchange system which enhances Ca influx and thus causes an inotropic effect in response to an increase in intracellular Na concentration.