The role of the complement system in the pathogenesis of the post-pericardiotomy syndrome (PPS) was evaluated in a prospective study by measuring the levels of complement (C) components, total haemolytic complement activity and circulating C3 breakdown products in serial plasma and serum samples of 45 patients undergoing open-heart surgery. A consistent reduction in the levels of C3 and C4 but not of factor B was seen on the second post-operative day. During the second post-operative week the antigenic levels of each C component increased significantly. At this time six patients developed the post-pericardiotomy syndrome. Circulating C3 conversion products (C3bi and C3c) were demonstrated in the plasma samples from five of these patients by the immunofixation technique, the mean conversion percentage being 14.3 +/- 10.6. The samples from 15 of the 39 other patients also showed C3 conversion, but the mean percentage was significantly lower (4.5 +/- 6.1%, P less than 0.05). Before the second post-operative week C3 conversion was rare in both groups. The C3d levels of plasma samples, as detected by rocket immunoelectrophoresis, followed a similar pattern. Reduced total haemolytic complement activity was found in three patients suffering from the PPS. These results suggest a role for complement in the non-infectious, inflammatory response during the late post-operative period after open heart surgery, and especially in the post-pericardiotomy syndrome.