The opioid mu-system is involved in brainstem-mediated respiratory control. Infants with intra-uterine growth restriction (IUGR) have more respiratory disorders in the early postnatal period. Using [(3)H]DAGO, a mu-selective ligand, and a computer-based image analysis of autoradiography, we compared the ontogeny and distribution of mu-opioid binding sites in the brainstem of IUGR and control rats in utero (E21), at birth (P0) and on postnatal days 1 (P1), P7, P10, P14 and P21. The ontogeny pattern was found to be similar in both groups. The density of the binding sites, which was low in E21, increased at P0, slightly declined at P1 and remained relatively constant thereafter. The distribution of DAGO-binding sites, also similar in both groups, was heterogeneous and was much denser in the dorsal areas of medulla and pons. In particular, binding sites were highly concentrated in nuclei involved in the cardio-respiratory function. However, DAGO-binding density was higher at all ages (except for P0 and P1) in IUGR than in control rats. Taken together, these results give at least a partial explanation for the effects of IUGR which lowers the Apgar score at birth and raises the incidence of respiratory disorders in infants.