We observed complement (C) activation during intermittent flow apheresis procedures (Haemonetics model 30) in four subjects, two of whom developed adult respiratory distress syndrome (ARDS). Actual C3 conversion during apheresis was illustrated by the finding of significantly elevated C3d levels (p less than 0.05) and of significantly increased alpha-1-antitrypsin/C3 ratios (p less than 0.05) in postapheresis serums. Similarly, marked granulocyte aggregating activity was found in these serums, indicative of the generation of significant amounts of the C-derived anaphylatoxin, C5a or C5a desarginine. A mean decrease of 59.75 percent in neutrophil count during the four procedures suggested sequestration of aggregated granulocytes in the pulmonary vasculature. Moreover, granulocytes activated by apheresis serums induced significant 51Cr leak from cultured human endothelial cells is vitro (p less than 0.001). We conclude that inflammatory C components produced during apheresis procedures may provoke granulocyte aggregation and embolization, leading to plugging of the pulmonary vasculature, and that apheresis-activated granulocytes may induce endothelial cytotoxicity, leading to the capillary leakage syndrome, characteristic of ARDS. Individual variability in C5a generation capacity or alterations in normal C5a clearing mechanisms may account for the low incidence of clinical C activation and true ARDS during apheresis. In these instances, high-dose steroids, which interfere with granulocyte-C interactions, may be beneficial.