The postnatal ontogeny of neuropeptide FF (NPFF) receptors in mouse brain was mapped by quantitative autoradiography using [125I](1DME)Y8Famide as selective radioligand. By day 14, the adult distribution of NPFF sites was established in almost all brain areas. The density of NPFF receptors reached adult levels between 14 and 28 days after birth, earlier than did mu or delta opioid receptors. During ontogeny, morphine analgesia was measured in hindpaw, forepaw and tail immersion tests (57 degrees C). An antinociceptive effect of morphine in the forepaw and tail immersion test was evident in 14-day-old but not in 7-day-old mice. In 14 and 21 day-old mice, the influence of (1DME)Y8Famide on morphine analgesia depended on the dose and on the particular test. A low dose of (1DME)Y8Famide inhibited morphine analgesia in the tail or hindpaw test, whereas a higher dose had either no effect (tail test) or increased morphine activity (hindpaw test). In adult mice, only the inhibition of morphine antinociception by (1DME)Y8Famide was observed. These observations revealed the establishment of an equilibrium between NPFF and opioid functions during ontogeny.