Dichloromethane (75092) (DCM) cardiotoxicity was studied in rats and in cultured rat cardiac myocytes. Ventricular myocytes were harvested from 2 to 4 day old male Wistar-rats and loaded with fura- 2, a fluorescent calcium-ion (Ca2+) sensitive dye. The myocyte preparations were incubated with up to 40.96 millimolar (mM) DCM. The preparations were paced at 1 Hertz by stimulation with a 60 volt potential for 10 minutes. The effects on electrically induced fluctuations of cytosolic free Ca2+ concentrations were assessed by spectrofluorometric analysis of changes in fura-2/myocyte binding. Wistar-rats anesthetized with 0.9 gram per kilogram urethane were instrumented with appropriate electrodes and transducers for measuring changes in cardiac rhythmicity. They were administered 3.1, 6.2, or 12.4 millimoles per kilogram (mmol/kg) DCM orally. Changes in heart rate, blood pressure, maximum velocity of left ventricular pressure (dP/dtmax), time to onset of dP/dtmax (To), and the Crayenbuhl index (CI) were determined before and after intravenous infusion of 50mg/kg calcium-chloride, which yielded arrhythmia inducing concentrations of Ca2+. Blood samples were collected and analyzed for DCM. In-vitro, DCM inhibited the electrically induced fluctuations in cytosolic free Ca2+ in a concentration dependent manner. The median inhibitory concentration was 18.1mM. The 40.96mM concentration completely inhibited the Ca2+ concentration transients and stopped the cardiac preparations from beating. In-vivo, treatment with 3.1, 6.2, and 12.4mmol/kg DCM produced blood DCM concentrations of 0.98, 1.54, and 1.6mM, respectively. DCM significantly decreased dP/dtmax in all animals. The 6.2 and 12.4mg/kg doses decreased the CI and heart rate and prolonged To. DCM did not affect blood pressure or induce any arrhythmias. Treatment with exogenous Ca2+, from calcium-chloride, induced second or third degree atrioventricular blocks and ventricular fibrillation. DCM protected against these effects. The authors conclude that the negative inotropic effects of DCM and its ability to protect against calcium-chloride induced arrhythmias are mediated by inhibition of Ca2+ dynamics in cardiac myocytes.