Circadian rhythms in mammals depend on the properties of cells in the suprachlasmatic nucleus (SCN). The retino-recipient core of the mouse SCN is characterized by vasoactive intestinal peptide (VIP) neurons. Expression within the SCN of VPAC2, a VIP receptor, is required for circadian rhythmicity Using transgenlc mice with β-galactosidase as a marker for VPAC2, we have phenotyped VPAC2, expressing cells within the SCN and investigated expression of the VPAC2 marker at sites previously shown to receive VIP-containing SCN efferents. In situ hybridization and immunohistochemistry demonstrated identical distributions for VPAC2 mRNA and β-galactosidase and coexpression of the two signals in the SCN. Double-label confocal immunofluorescence identified β-galactosidase in 32% of the VIP and 31% of the calretinin neurons In the SCN core. Of the arginine-vasopressin neurons that characterize the SCN shell, 45% expressed β-galactosidase. In contrast, this marker was not apparent in astrocytes within the SCN core or shell. Cell bodies containing β-galactosidase were detected at sites reportedly receiving VIP-containing SCN efferents, including the subparaventricular zone and lateral septum and the anteroventral periventricular, preoptic suprachiasmatic, medial preoptic and paraventricular hypothalamic nuclei. The detection of a marker for VPAC2 expression in the SCN in almost one-third of the VIP and calretinin core neurons and nearly half of the arginine-vasopressin shell neurons and also in cell bodies at sites receiving VIP-immunoreactive projections from the SCN indicates that VPAC 2 may contribute to autoregulation and/or coupling within the SCN core and to the control of the SCN shell and sites distal to this nucleus.