We studied 51 sera from patients with systemic lupus erythematosus to determine the relationship of their anti-phospholipid activity to their anti-erythrocyte and complement activation properties. Forty-nine per cent of the sera had anti-phospholipid activity as demonstrated by ELISA using a panel of anionic phospholipids, and most of these also bound to neutral phospholipids, albeit to a lesser extent. A cellular radioimmunoassay was used for the detection of immunoglobulin and C3 binding to normal erythrocytes (intact, enzyme-treated or glutaraldehyde-fixed) following incubation with patient sera. The levels of IgG anti-phospholipid correlated with hypocomplementaemia and with immunoglobulin binding (paralleled by a deposition of C3 fragments) to the three types of erythrocytes, although most strongly to fixed cells. Immunoglobulin binding to intact erythrocytes correlated primarily with reactivity against neutral phospholipids. The specificity for phospholipid epitopes of immunoglobulin adsorbed onto erythrocytes was confirmed by acid elution followed by testing in ELISA. These data suggest that some anti-phospholipid antibody subsets may bind to erythrocytes in vivo, thus accounting for the observed association of these antibodies with positive direct antiglobulin tests.