We measured Ca2+uptake by sarcoplasmic reticulum prepared from left ventricular myocardium obtained from six nonfailing human hearts and nine excised hearts from patients with class IV idiopathic dilated cardiomyopathy. Ca2+uptake had a Vmaxof 593 ± 82 nmol/mg-min, a K0.5of 0.68 ± 0.07 μM, and an nHILLof 1.7 ± 0.1 in the nonfailing hearts. The corresponding values in the excised failing hearts were 593 ± 36 nmol/mg-min, 0.63 ± 0.03 μM, and 1.6 ± 0.1. The β-receptor density in crude sarcolemma prepared from left ventricular myocardium was 110.0 ± 15.3 fmol/mg in the unmatched donors and 52.1 ± 4.5 fmol/mg in the excised failing hearts. These results suggest that abnormal Ca2+handling in idiopathic dilated cardiomyopathy in humans is not the result of any intrinsic alteration of Ca2+uptake by sarcoplasmic reticulum.