Microbicidal and cytocidal products of the respiratory burst and integrin adhesion molecule expression have been studied in monocytes from patients who received rHuGM‐CSF during regeneration after high‐dose chemotherapy. In this study, administration of rHuGM‐CSF after high‐dose chemotherapy significantly augmented the secretion of inducible products of the monocyte respiratory burst. Monocyte activation persisted for several weeks after the cessation of GM‐CSF therapy. Under in vitro conditions that mimicked gram‐negative (LPS) and gram‐positive (opsonized Staphylococcus aureus) sepsis, the monocyte responded to such stimulation by exhibiting an enhanced release of hydrogen peroxide at both regeneration and several weeks later (P < 0–001). Similarly, GM‐CSF administration significantly augmented the phenotypic expression of the /32‐integrin adhesion molecules and allowed the leucocyte‐specific selectin, LAM‐1, and the /J2‐integrins to respond normally to inflammatory stimulation by LPS. We further present evidence that GM‐CSF therapy restored the otherwise refractory status of monocytes to inflammatory stimulation that existed in those patients given chemotherapy alone. The restoration of monocyte responsiveness by GM‐CSF following high‐dose chemotherapy could be a potentially valuable and hitherto not described action of rHuGM‐CSF on monocyte function. We conclude that administration of GM‐CSF may have the potential for restoring as well as augmenting the anti‐microbial and anti‐tumour function of the monocyte after high‐dose chemotherapy.