Previous investigators have established that complement activation occurs in patients with systemic lupus erythematosus (SLE). Utilizing a new rapid method, an ELISA for C3d as a measure of activation products, 83 SLE plasmas and 24 controls were assayed. A retrospective correlation of C3d levels with the clinical assessment defined 4 subgroups of SLE patients: Group 1--clinically well with normal C3d levels (25%), Group 2--clinically ill with elevated C3d levels (34%), Group 3--clinically well with elevated C3d levels (39%), the largest group, and Group IV--clinically ill with normal C3d levels (2%). In the group of overtly ill patients with elevated C3d levels (Group 2) who were studied serially, C3d levels correlated with disease activity, suggesting that elevated C3d levels may be a marker for active SLE. Further prospective study is required to determine the significance of elevated C3d levels in clinically well patients.