Anticardiolipin antibodies (aCL) were evaluated in 65 consecutive patients with systemic lupus erythematosus using an enzyme linked immunoassay (ELISA) and were detected in 14 (22%). There was no association of aCL with active disease, specific clinical manifestations, high DNA binding or circulating immune complex levels. The presence of aCL was associated with lupus anticoagulant activity (p less than 0.001), positive VDRL (p less than 0.05), and lower mean platelet counts (p less than 0.05) and C3 levels (p less than 0.05). Both aCL and lupus anticoagulant activity were associated with positive Coombs' (p less than 0.01) and low C4 (p less than 0.01 and p less than 0.05, respectively). Analysis of red blood cell (RBC) eluates and absorption studies using fixed RBC suggested that some aCL may act as anti-RBC antibodies, likely directed at membrane phospholipid epitopes. Furthermore, we hypothesize that complement may participate as a cofactor maximizing lupus anticoagulant activity.