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The aggregation capacity of human erythrocytes lies between that of the non-aggregating bovine erythrocytes and the remarkably aggregating equine ones. As the ability to aggregate is attributed to cell factors and the composition of the plasma proteins, the role that plasma proteins play in the aggregation process in these three species was studied. Washed erythrocytes were suspended in phosphate-buffered saline (PBS; pH 7.4, 300 mOsm/L) plus polyvinylpyrrolidone (PVP) in a suitable concentration to obtain an average intensity of aggregation (control media). The superimposed effect of replacing 80% of the medium by either autologous plasma, serum or albumin solution was studied. The plasma proteins appeared to enhance aggregation by human and equine erythrocytes, but impaired this process in bovine erythrocytes. Some evidence was obtained supporting the existence of serum factors capable of reducing aggregation of erythrocytes in cattle and it was concluded that the non-aggregating behaviour of bovine erythrocytes may be due to the cells interacting particularly with the macromolecules in the serum.