The anesthetics chloroform, halothane, ethyl ether, and sodium pentobarbital, which have negative inotropic properties, were examined for effects on the calcium pump of the sarcoplasmic reticulum of the dog myocardium. Chloroform and sodium pentobarbital, at concentrations similar to those depressing cardiac contractility, inhibited calcium uptake. The concentration of halothane required to inhibit calcium uptake was ten times greater than that required to produce depression of contractility. Ether at concentrations eight times greater than those producing inhibition of contraction was completely without effect on calcium uptake. Chloroform and halothane depressed calcium uptake and calcium-stimulated ATPase activity in parallel, indicating that these agents do not uncouple transport from ATP hydrolysis. Sodium pentobarbital, in contrast, uncoupled transport from ATP hydrolysis.