The effects of priming monocytes from septic patients with granulocyte-macrophage colonystimulating factor (GM-CSF) ex vivo were investigated. Monocytes from septic patients had depressed plasma GM-CSF and dysregulated levels of other cytokines compared with normal subjects. Membrane expression of CD71 and HLA-DR were depressed, and monocytes were anergic to lipopolysaccharide (LPS) stimulation in vitro, which was associated with spontaneous and accelerated activation-induced apoptosis by LPS. Priming monocytes with GM-CSF ex vivo augmented membrane cytokine expression, CD71, and HLA-DR. GM-CSF priming augmented cytokine secretion in response to LPS stimulation, restored cytokine secretion in monocytes from septic patients, and reversed their predilection to undergo apoptosis. Thus, monocyte dysfunction in septic shock is associated with depressed plasma levels of GM-CSF and enhanced apoptosis; however, GM-CSF stimulation ex vivo restored normal monocyte function and cytokine secretion by a mechanism that may depend on abrogating apoptosis.