This study was conducted to investigate myocardial excitation-contraction coupling in the fetus of the diabetic rabbit (FDM). On day 14 of gestation, diabetes was induced in pregnant rabbits by alloxan injection. On day 28 of gestation, mechanical function of the fetal myocardium was determined in the isolated arterially perfused heart preparation. At 1.5 mM [Ca2+]o(control), the force of myocardial contraction in FDM was not significantly dfferent from that in the control fetus. At higher [Ca2+]o, developed tension and maximal rate of tension development [+dT/dt (max)] in FDM were significantly greater than in the control fetus. High [Ca2+]ocaused significant increases in resting tension and half-relaxation time (toxic effects) in the control fetus, but not in FDM. Perfusion with lanthanum (known to displace sarcolemma-bound Ca2+and block sarcolemmal Na-Ca exchange) decreased developed tension and +dT/dt (max) and increased resting tension and these effects in FDM were significantly less than in the control fetus. Perfusion with manganese (known to displace Ca2+from intracellular sites) also decreased developed tension and +dT/dt (max) and increased resting tension, and these effects were similar in the two groups. The myofibrillar ATPase activities at various calcium concentrations were not different between the two groups. The rates of Ca2+uptake by mitochondria and sarcoplasmic reticulum were similar in the two groups. These data suggest that in FDM the inotropic effect of Ca2+is greater and the toxic effect of Ca2+is less than in the control fetus. This difference may be due, at least in part, to a sarcolemmal alteration induced by the maternal diabetes.