<i>Background/Aims:</i> Circadian control of behavior and physiology is a central characteristic of all living organisms. The master clock in mammals resides in the hypothalamus, where the suprachiasmatic nucleus (SCN) synchronizes daily rhythms. A variety of recent evidence indicates that the neuropeptide vasoactive intestinal peptide (VIP) is critical for normal functioning of the SCN. The aim of our study was to examine the possible role of VIP in driving circadian rhythms in the hypothalamic-pituitary-adrenal axis. <i>Methods:</i> Circulating ACTH and corticosterone concentrations were determined by round-the-clock sampling under diurnal and circadian conditions. The responsive aspects of the hypothalamic-pituitary-adrenal axis were tested by application of acute stress by footshock and light. <i>Results:</i> We demonstrate that the circadian rhythms in ACTH and corticosterone are lost in VIP-deficient mice. The ability of light to induce a corticosterone response was also compromised in the mutant mice, as was photic induction of <i>Per1</i> in the adrenal glands. In contrast, the acute stress response was apparently unaltered by the loss of VIP. <i>Conclusion:</i> Thus, our data demonstrate that VIP is essential for the circadian regulation of an otherwise intact hypothalamic-pituitary-adrenal axis.