Atrial fibrillation (AF) is common after cardiac surgery. Abnormal conduction is an important substrate for AF. We hypothesized that atrial inflammation alters atrial conduction properties. Normal mongrel canines (n=24) were divided into 4 groups consisting of anesthesia alone (control group); pericardiotomy (pericardiotomy group); lateral right atriotomy (atriotomy group); and lateral right atriotomy with antiinflammatory therapy (methylprednisolone 2 mg/kg per day) (antiinflammatory group). Right atrial activation was examined 3 days after surgery. Inhomogeneity of conduction was quantified by the variation of maximum local activation phase difference. To initiate AF, burst pacing was performed. Myeloperoxidase activity and neutrophil cell infiltration in the atrial myocardium were measured to quantify the degree of inflammation. The inhomogeneity of atrial conduction of the atriotomy and pericardiotomy groups was higher than that of the control group (2.02+/-0.10, 1.51+/-0.03 versus 0.96+/-0.08, respectively; P<0.005). Antiinflammatory therapy decreased the inhomogeneity of atrial conduction after atriotomy (1.16+/-0.10; P<0.001). AF duration was longer in the atriotomy and pericardiotomy groups than in the control and antiinflammatory groups (P=0.012). There also were significant differences in myeloperoxidase activity between the atriotomy and pericardiotomy groups and the control group (0.72+/-0.09, 0.41+/-0.08 versus 0.18+/-0.03 DeltaOD/min per milligram protein, respectively; P<0.001). Myeloperoxidase activity of the antiinflammatory group was lower than that of the atriotomy group (0.17+/-0.02; P<0.001). Inhomogeneity of conduction correlated with myeloperoxidase activity (r=0.851, P<0.001). The degree of atrial inflammation was associated with a proportional increase in the inhomogeneity of atrial conduction and AF duration. This may be a factor in the pathogenesis of early postoperative AF. Antiinflammatory therapy has the potential to decrease the incidence of AF after cardiac surgery.