The main olfactory bulb (MOB) receives a dense projection from the pontine nucleus locus coeruleus (LC), the largest collection of norepinephrine (NE)-containing cells in the brain. LC is the sole source of NE innervation of MOB. Previous studies of the actions of exogenously applied NE on mitral cells, the principal output neurons of MOB, are contradictory. The effect of synaptically released NE on mitral cell activity is not known, nor is the influence of NE on responses of mitral cells to olfactory nerve inputs. The goal of the present study was to assess the influence of LC activation on spontaneous and olfactory nerve-evoked activity of mitral cells. In methoxyflurane-anesthetized rats, intracoerulear microinfusions of acetyicholine (ACh) (200 mM; 90-120 nl) evoked a four- to fivefold increase in LC neuronal discharge, and a transient EEG desynchronization and decrease in mitral cell discharge. LC activation increased excitatory responses of mitral cells evoked by weak (i.e., perithreshold) nasal epithelium shocks (1.0 Hz) in 17/18 cells (mean Increase = 67%). The discharge rate of mitral cells at the time that epithelium-evoked responses were increased did not differ significantly from pre-LC activation baseline values. Thus, changes in mitral baseline activity do not account for the increased response to epithelium stimulation. These findings suggest that increased activity in LC-NE projections to MOB may enhance detection of relatively weak odors.