Ricin, a toxic lectin from the castor bean, affects the cardiovascular system. Because calcium is very important in cardiotoxicity and cell intoxication, we studied the effects of ricin pretreatment to rabbits on basal intracellular calcium levels and calcium uptake and release from isolated papillary muscle, microsomes, and mitochondria. An increase in basal intracellular calcium levels was observed. Rich pretreatment nearly doubled the intracellular-free Caz+ concentration as measured by fura-2 fluorescence microscopy in isolated myocytes ( p = 0.002). Rich did not alter basal calcium efflux in isolated papillary muscles. However, ricin inhibited the NE-induced calcium efflux (expressed as fractional eMux ratios) in papillary muscles from rabbits receiving the minimum lethal dose of ricin at 25-35 minutes ( p = 0.002 and 0.003, respectively). Rich depressed basal calcium uptake into isolated papillary muscles at 5 minutes (mean f SEM, pmoYg wet weight) (control: 3.68 f 0.57; ricin: 2.31 f 0.28, p = 0.045, n = 6). Ricin pretreatment significantly depressed calcium uptake into microsomes (mean f SEM, pmoYg protein) (control: 9.9 f 1.9; ricin: 3.1 f 1.9, p = 0.025, PI = 6). Calcium uptake into mitochondria was increased at the beginning (2 minutes, p = 0.048), but not thereafter. Thus, administration of ricin disturbed calcium homeostasis in the rabbit heart, which may be at least partially responsible for altering cardiac function and myocardial cell death.