—Chronic atrial fibrillation (AF) is characterized by decreased atrial contractility, shortened action potential duration, and decreased accommodation of action potential duration to changes in activation rate. Studies on experimental animal models of AF implicate a reduction in L-type Ca²⁺ current (I_Ca) density in these changes. To evaluate the effect of AF on human I_Ca, we compared I_Ca in atrial myocytes isolated from 42 patients in normal sinus rhythm at the time of cardiac surgery with that of 11 chronic AF patients. I_Ca was significantly reduced in the myocytes of patients with chronic AF (mean −3.35±0.5 pA/pF versus −9.13±1.0 pA/pF in the controls), with no difference between groups in the voltage dependence of activation or steady-state inactivation. Although I_Ca was lower in myocytes from the chronic AF patients, their response to maximal β-adrenergic stimulation was not impaired. Postoperative AF frequently follows cardiac surgery. Half of the patients in the control group (19/38) of this study experienced postoperative AF. Whereas chronic AF is characterized by reduced atrial I_Ca, the patients with the greatest I_Ca had an increased incidence of postoperative AF, independent of patient age or diagnosis. This observation is consistent with the concept that calcium overload may be an important factor in the initiation of AF. The reduction in functional I_Ca density in myocytes from the atria of chronic AF patients may thus be an adaptive response to the arrhythmia-induced calcium overload.