In mammals, the main circadian pacemaker is located in the suprachiasmatic nucleus (SCN) and its most potent synchronizer is the daily variation of the intensity of light. However, other nonphotic cues, such as timed food restriction, can induce changes in the circadian rhythms, leading also to the appearance of a food-entrained oscillator. The present study was designed to establish if the alterations of the circadian rhythms induced by timed hypocaloric food restriction are accompanied by structural changes in the SCN. Two groups of adult rats, both maintained on 12-h light/12-h dark cycles, were used; in one group, animals had permanent free access to food, whereas in the other they were subjected to a restricted hypocaloric early morning feeding during 7 months. Using stereological techniques and in situ hybridization, we have examined the structure of the SCN and the synthesis and expression of vasopressin (AVP) and vasoactive intestinal peptide (VIP). The volume of the SCN and the total number of neurons did not vary between the two groups. However, the total number of AVP- and VIP-immunoreactive neurons and the AVP and VIP mRNA levels were significantly decreased in timed hypocaloric food-restricted animals. The results indicate that timed hypocaloric food restriction has led to changes of AVP and VIP content of the neurons. They furthermore suggest the existence of a coupling between the food-entrainable oscillator and the light-entrainable pacemaker.