The influence of plasma proteins on erythrocytes was studied by interference microscopy, scanning electron microscopy (SEM), and by Westergren erythrocyte sedimentation rate (ESR). Albumin kept erythrocytes dispersed as discoid spheres. Fibrinogen seemed responsible for the rouleaux phenomenon, but needed the co-influence of an immunoglobulin to induce rouleaux type of aggregates and high ESR. IgG, IgA and IgM caused immunologic type of aggregates. Albumin acted synergistically with fibrinogen and immunoglobulins. Normal blood contained a network of rouleaux, which probably explained the low normal ESR. High ESR was either due to rouleaux type aggregates where fibrinogen was dominant, or immunologic type aggregates where IgG, IgA or IgM were dominant proteins. Cold agglutinin disease showed normal blood morphology and normal ESR at 37 degrees C and immunologic type aggregates and high ESR at 25 degrees C.