With the exception of fibrinogen, immunoglobulins, and albumin, little information is available on the effect of acute-phase proteins on erythrocyte aggregation. The objective of this study was to investigate the effects of haptoglobin (Hp), C-reactive protein (CRP), ceruloplasmin (Cp), alpha 1-acid glycoprotein (alpha 1-AGP), and alpha 1-antitrypsin (alpha 1-AT) on the aggregation kinetics and shear resistance of erythrocyte aggregates. The plasma concentration of these proteins was measured in 20 healthy individuals and kept unchanged while the concentration of the protein tested was increased. Adding Hp to concentrations between 2.78 and 4.99 g/l resulted in a significant progressive increase in aggregation kinetics compared with controls. An elevation of the shear resistance of the aggregates was found for CRP at a concentration of 0.438 g/l. By an increase in the concentration of Cp from 4.40 to 9.39 g/l, the aggregation kinetics and the adhesive forces between erythrocytes were significantly increased: No effect on erythrocyte aggregation was observed for alpha 1-AGP, alpha 1-AT, and Cp at concentrations of 2.85, 3.97, and 2.43 g/l, respectively. The molecular mass of the acute-phase proteins, their configuration, and the presence of specific receptors on the erythrocyte membrane are postulated as possible factors influencing erythrocyte aggregation.