Decreased cardiac contractility occurs in endotoxicosis, but little is known about the ionic mechanism responsible for myocardial dysfunction. In this study, we examined the changes in Ca2⁢ and K⁢ currents in cardiac myocytes from endotoxin-treated rat. Ventricular myocytes were isolated from normal and endotoxemic rats (ex vivo), that were treated for 10 hours with Salmonella enteritidis lipopolysaccharides (LPS; 1.5 mg/kg) intravenously. Normal cardiac myocytes were also incubated for 6 hours with 200 ng/ml LPS (in vitro). L-type Ca2⁢ current (ICa,L) and transient outward K⁢ current (Ito) were measured using whole cell patch clamp techniques. Peak ICa,L was reduced in endotoxemic myocytes (ex vivo; 6.00.4 pA/pF, P＜0.01) compared to normal myocytes (control; 10.90.6 pA/pF). Exposure to endotoxin in vitro also attenuated ICa,L (8.40.4 pA/pF, P＜0.01). The amplitude of Ito on depolarization to 60 mV was reduced in endotoxin treated myocytes (16.51.5 pA/pF, P＜0.01, ex vivo; 20.00.9 pA/pF, P＜0.01 , in vitro) compared to normal myocytes (control; 24.71.0 pA/pF). There was no voltage shift in steady-state inactivation of ICa,L and Ito between groups. These results suggest that endotoxin reduces Ca2⁢ and K⁢ currents of rat cardiac myocytes, which may lead to cardiac dysfunction.