This paper is an account of the afferent and efferent projections of the nucleus sphericus (NS), which is the major secondary vomeronasal structure in the brain of the snake Thamnophis sirtalis. There are four major efferent pathways from the NS: 1) a bilateral projection that courses, surrounding the accessory olfactory tract, and innervates several amygdaloid nuclei (nucleus of the accessory olfactory tract, dorsolateral amygdala, external amygdala, and ventral anterior amygdala), the rostral parts of the dorsal and lateral cortices, and the accessory olfactory bulb; 2) a bilateral projection that courses through the medial forebrain bundle and innervates the olfactostriatum (rostral and ventral striatum); 3) a commissural projection that courses through the anterior commissure and innervates mainly the contralateral NS; and 4) a meager bilateral projection to the lateral hypothalamus. On the other hand, important afferent projections to the NS arise solely in the accessory olfactory bulb, the nucleus of the accessory olfactory tract, and the contralateral NS. This pattern of connections has three important implications: first, the lateral cortex probably integrates olfactory and vomeronasal information. Second, because the NS projection to the hypothalamus is meager and does not reach the ventromedial hypothalamic nucleus, vomeronasal information from the NS is not relayed directly to that nucleus, as previously reported. Finally, a structure located in the rostral and ventral telencephalon, the olfactostriatum, stands as the major tertiary vomeronasal center in the snake brain. These three conclusions change to an important extent our previous picture of how vomeronasal information is processed in the brain of reptiles.