The efferent and centrifugal afferent connections of the main olfactory bulb (MOB) of the mouse were studied by orthograde and retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). MOB projects ipsilaterally to the anterior olfactory nucleus, taenia tecta, anterior hippocampal continuation, indusium grisium, olfactory tubercle, and the lateral and medial divisions of the entorhinal area. In the region of the anterior one-half to two-thirds of the posterior division of the insular cortex the projection from MOB extends into the insular cortex. The only efferent projection of MOB to the contralateral half of the brain was to the anterior olfactory nucleus. All efferent projections of MOB, thus, are to telencephalic structures. By contrast the centrifugal afferents to MOB originate from every major division of the neuraxis. Neurons projecting to the bulb were found ipsilaterally in all divisions of the anterior olfactory nucleus (AON). In some cases, labeling in the external division of AON was weak or absent. In the contralateral AON, pars externa was the most intensively labeled sub-division. Retrogradely labeled neurons were also present in all other subdivisions of the contralateral AON but were fewer in number and less heavily labeled than in the ipsilateral AON. Ipsilaterally, positive neurons were also present in taenia tecta, and the anterior hippocampal continuation. There was profuse retrograde labeling of neurons in the entire extent of the ipsilateral piriform cortex (PC). There was a rostral to caudal gradient of labeling in PC with more positive neurons in rostral than caudal parts. Labeled neurons were present in the lateral entorhinal cortex LEC and in the transitional cortex between LEC and PC. Very heavy retrograde labeling was present in the nuclei of the horizontal and vertical limbs of the diagonal band (HDB and VDB). More cells were labeled in HDB than in VDB. Neurons were labeled in the ipsilateral nucleus of the lateral olfactory tract (NLOT) and, when the injection spread into the accessory olfactory bulb, labeled neurons were present ventral to NLOT in accessory NLOT. A few lightly labeled neurons were always present in the posterolateral and medial cortical amygdaloid areas. Neurons were labeled in the zona inserta and scattered throughout several hypothalamic nuclei. There was massive retrograde labeling of neurons in the locus coeruleus and neurons were abundantly labeled in the dorsal and medial raphe nuclei and nucleus raphe pontis. In general, the labeling of MOB connections was more extensive than that which has been reported in closely related species.(ABSTRACT TRUNCATED AT 400 WORDS)