Neuropeptide Y (NPY) is increased in the hypothalamus during lactation. To investigate the role of the NPY Y5 receptor during lactation, an antisense oligodeoxynucleotide (ODN) targeted to the NPY Y5 receptor, an equivalent scrambled ODN or vehicle, was chronically infused into the 3rd ventricle of lactating rats from day 8 postpartum. Y5 antisense ODN treatment reduced Y5 positive cell number in the paraventricular nucleus and resulted in significant reductions in food intake and litter growth. Litters from pair-fed vehicle treated dams gained significantly more weight than the litters of Y5 antisense ODN treated dams suggesting that decreased maternal food intake is not the only mechanism involved in suppressing litter weight gain. When mother-litter interaction was examined on day 13 pp, Y5 antisense ODN treated dams spent significantly less time on the nest and had significantly shorter nest bouts. These results suggest that in addition to regulating feeding behaviour, the Y5 receptor subtype may have previously unrecognised roles in the control of nesting behaviour during lactation with subsequent effects on litter growth rates.