Left ventricular (LV) function and Na+, K(+)-ATPase activity were studied in rabbit failing heart (FH) obtained by a double pressure plus volume overload which increased LV/body weight ratio by 58%. Ouabain (10(-6) M) increased peak dP/dt by 69% in control hearts (CH) but not in FH. Na+, K(+)-ATPase activity was similar in FH and in CH but the affinity of Na+, K(+)-ATPase for ouabain was significantly higher in CH than in FH (IC50: 2 microM vs 90 microM). The blunted LV contractile response to ouabain in FH is attributed to a decreased Na+, K(+)-ATPase affinity to ouabain and not to a decreased receptor density.