Blood cells from patients with systemic lupus erythematosus (SLE) and from healthy control subjects were studied for their ability to bind exogenous immune complexes. Cells were mixed with experimental complexes (prepared from 125I-radiolabeled bovine serum albumin [BSA] and guinea pig antiserum to BSA) after incubation of the complexes with autologous serum in variable proportions. Unfractionated blood cells from SLE patients bound fewer added complexes (mean +/- SD = 39.8% +/- 12.9%) than cells from normal controls (mean +/- SD = 63.6% +/- 9.5%) (p less than 0.001); as much as 128-fold (mean = 23-fold) higher (p less than 0.01) proportions of serum to complex were required to optimize the lower binding. When SLE blood cells were mixed with complexes preincubated with normal sera instead of autologous SLE sera, SLE cells bound increased amounts of added complexes, and binding was optimal at the same lower proportions of serum to complex as for normal cells. When normal cells were mixed with complexes preincubated with compatible SLE sera in place of endogenous normal sera, binding to normal cells decreased to SLE levels, and the same higher proportions of serum to complex were required to optimize the lower binding as for the SLE cells. Similar results were obtained when binding to purified mononuclear cell preparations from SLE patients and controls was studied. When comparative studies were performed at high complex-to-cell ratios with complexes prepared using normal sera, SLE cells bound fewer complexes per cell than normal cells. These results indicate that although abnormalities in SLE cells are demonstrable, the major factor accounting for aberrant interaction between immune complexes and SLE cells resides in alterations in SLE sera.