In mammals the main olfactory bulb (MOB) receives afferent sensory glutamatergic receptor neurons and sends efferent fibres direct to different structures. Recent physiological properties, involving MOB, in particular regeneration research and neurogenesis have been shown (1). In addition, the MOB receives a large number of projections from different CNS zones. A dendrodendritic reciprocal synapse is proposed to understand the olfactory mitral cell and granular cell syncronization. A dendrodendritic reciprocal synapse provides a recurrent excitatory connection in the olfactory bulb (2). Previous studies have demonstrated different interactions between the olfactory bulb and different cortical and subcortical zones in relation to discrimination and integration of olfactory inputs with monosynaptic and polysynaptic pathways: this determines the access to hippocampal formation. For example, the olfactory lobes of Alzheimer’s patients exhibit oxidative stress and it is well known that olfactory dysfunction frequently accompanies neurodegeneration. Different neurotransmitters are involved in MOB projections: cholinergic projections to the hippocampus have been proposed to serve as the pacemaker for the hippocampal theta rhythm (3). Our electrophysiological and neuroanatomical studies have demonstrated that interpeduncular neurons (IPN) are influenced by olfactory bulb neurons (4) with monosynaptic pathway. This projection is evoked by natural olfactory stimulation of the olfactory receptor and is monosynaptically connected to the hypoglossal nucleus. In the present study, we used a fluorescent retrograde technique in the adult rat to identify direct branching axonal projections from the olfactory bulb to the IPN and to amygdaloid nucleus; immunohistochemical methods were used to identify which neurotransmitters or neuropeptides are involved in these projections. Ten male Wistar rats were anaesthetized with chloral hydrate (400 mg/kg i.p.). Two fluorescent tracers were injected into the same rat: fluoro gold (FG) was injected into the basomedial amygdaloid nucleus on one side, and rhodamine-labelled beads (RLB) into the interpeduncular nucleus of the same side. Four series of MOB coronal sections (35-40μm) were cut on a Reichert cryostat and observed with a fluorescent microscope and immunocytochemically processed with specific antibodies. Vasoactive intestinal peptide (VIP), substance P (SP) and neuropeptide Y (NPY) neurons were revealed by immunocytochemical detection of polyclonal antibodies. In the MOB small (10-25μm) single FG-mitral cells and single RBL mitral cells were found. Double-projecting neurons were distributed in the entire mitral layer. The results demonstrate that pools of neurons in the MOB show collateral projections to the amygdaloid and IPN expressing different neuropeptides.