Antigen:antibody complexes, prepared with 125I-bovine serum albumin and guinea or rabbit antibody, were added to serum and blood cells from normal individuals and binding studied. When antigen:antibody were pre-incubated with serum in varying proportions for 30 min at 37 degrees C and then mixed with washed unseparated cells, binding increased to a maximum (70% of added complexes) and then decreased as serum to antigen:antibody proportions were increased. Separation of cells revealed that following maximal binding to unfractionated cells, complexes were predominantly associated with red blood cells (RBC), even though complexes bound less per cell to RBC than to white blood cells following addition of complexes to separated cells. Binding to RBC was reduced by zymosan treatment of serum and abolished by heat inactivation or substitution of non-primate RBC (known not to possess C3b receptors) for human RBC, indicating that binding to human RBC was via C3b receptors. When antigen:antibody were incubated at 37 degrees C directly with serum and unfractionated blood cells, maximal binding occurred after 2-4 minutes and declined thereafter. Identical kinetics were observed when purified RBC were substituted for whole blood cells. When diluted or hypocomplementemic (systemic lupus erythematosus) serum was substituted for neat serum, maximal binding was delayed and sustained. Our findings suggest that RBC in human blood can compete with other cell types for immune complexes at that stage during the sequence of reactions between complexes and complement when complexes are able to bind to C3b receptors.