The significance of the level of circulating 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphorylcholine (C16-PAF, platelet-activating factor) in relation to transient neutropenia during hemodialysis with cuprophane membranes was examined. The neutrophil count was transiently and significantly decreased at 30 min after the start of hemodialysis, and it then gradually recovered during the period from 60 to 240 min after the start. Mirror image changes were observed in the circulating levels of C3a and C5a, suggesting that the decrease in the neutrophil count was triggered by activation of the complement factors. The circulating level of C16-PAF, although being similar to the basal level after 30 min of hemodialysis, was significantly increased after 60 and 120 min of hemodialysis. These data indicate that the increase in the circulating PAF level is not a direct cause of the transient decrease in the neutrophil count, but may be the result of activated neutrophils during hemodialysis with cuprophane membranes.