It has been difficult to study the metabolism and function of the heart in uremia in the intact human or animal because of the numerous uncontrolled factors introduced by the uremic state. The present investigation proposes to study hearts of uremic rats under conditions that are relatively independent of these variables. Hearts of acute and chronically uremic rats will be studied. Metabolism (oxygen, carbohydrates, lipids, and high energy phosphates) will be investigated in homogenates, perfused arrested hearts and be correlated with function of the heart as a pump and as a muscle in the isolated working rat heart. The effects of uremic serum and individual products of uremia (on hearts from normal rats) will also be investigated in the same experimental systems. Mechanical findings will be confirmed in studies of papillary muscles. Enzymatic and calcium control adaptive mechanisms will be investigated in an attempt to explain any of the mechanical or metabolic differences observed.