We studied the effects of granulocyte-macrophage colony stimulating factor (GM-CSF) on the classical behavioral test of scopolamine-induced amnesia for a passive avoidance response in the mouse. Pre-training intraperitoneal administration of this cytokine (1.25, 2.5, 5.0 or 10 micrograms/mouse) partially, although significantly, reduced the amnesic action of the muscarinic receptor antagonist. The peripheral administration of a specific interleukin-1 receptor antagonist (IL-1 ra, 50 micrograms/mouse i.p.) blocked the effect of GM-CSF. Our results suggest that GM-CSF is able to exert neuromodulatory actions and that it is involved (probably via IL-1) in the interactions between the immune system and the central nervous system.