In this study we describe the time-dependent effects of a high dose (750 ~g/mli24 hr) continuous infusion of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on monocyte number, cytokine release, and superoxide anion production. Blood was taken from patients prior to rhGM-CSF infusion (day 0), and on days 1,7, and 14 of infusion. The mean concentration of monocytes per ml of blood increased progressively from 4.3 x lo5 on day 0 to 21 x lo5 on day 14 of infusion. There was no significant change in the basal release of tumor necrosis factor u (TNF-U) or interleukin 1 p (IL-1 p) induced by rhGM-CSF. However, the lipopolysaccharide (LPS)-stimulated release of TNF-u by monocytes increased significantly on day 1 of infusion, and by day 14 had increased 8-fold. 11-1 p release from LPS-stimulated monocytes increased slightly by day 7, and by almost 10-fold by day 14 of infusion. When maximally stimulated with phorbol dibutyrate, the monocytes demonstrated an increased (although not significant) capacity to produce superoxide anion on days 7 and 14 of infusion. No change in basal superoxide anion production was seen at any day of infusion. These GM-CSF-induced changes in stimulated cytokine and superoxide anion release could not be reproduced by treating monocytes with rhGM-CSF in vitro. In summary, a two week, high dose infusion of rhGM-CSF resulted in increases in circulating rnonocyte concentration, and in the stimulated release of TNF-u and IL-lp, and superoxide anion production from these monocytes. These primed monocytes could enhance the ability of neutropenic patients to fight infection. ic 1993 Wiley-Lies, Inc.