IFN-γ redirects cell fate decisions in granulocytic-monocytic progenitors (GMPs) during infection. In homeostatic conditions, G-CSF and M-CSF regulate the monocytic and granulocytic output from GMPs. During viral infections, IFN-γ, produced by activated Th1 T cells, affects GMP differentiation by: (1) up-regulation of the expression of PU.1 and IRF-8, transcription factors driving monocytic differentiation, and (2) induction of SOCS3, which antagonizes G-CSF–dependent STAT3 phosphorylation. The overall result is a skewing of myelopoiesis toward monopiesis at the expense of granulopiesis.