Two micro enzyme immunoassays (microEIA) for circulating immune complexes (CICs) are described. The Raji cell microEIA was similar in sensitivity, reproducibility and specificity to the Raji radioimmunoassay. The F(ab')2 anti-C3 microEIA was comparable to the 2 Raji cell assays. The 2 microEIAs for CICs were used to analyze sera from patients with systemic lupus erythematosus (SLE), the acquired immune deficiency syndrome (AIDS) and from hemophiliacs with AIDS-like symptoms. The microEIAs were very sensitive in detecting CICs in pathologic sera. In contrast, only 3% of normals (n = 30) were positive in the Raji microEIA while none were positive in the F(ab')2 anti-C3 microEIA. The initial high positivity of some normals (9/30) in the F(ab')2 microEIA was due to bovine serum albumin (BSA)-anti-BSA immune complex formation in vitro and was corrected when human albumin was used in buffer preparation instead of BSA. The reagents required for the microEIAs are more stable and less expensive than those required for the RIAs and the need for facilities to deal with 125-labeling and disposal is avoided.