Opioid receptor binding of morphine-6-beta-D-glucuronide (M6G), morphine and [3H][D-Ala2,N-methylPhe4-Glyol5]enkephalin (DAMGO) were determined in neonatal guinea pigs. Pontomedullary membranes specifically bound [3H]DAMGO, which was displaced by M6G and morphine. The KI for M6G and morphine were 15.1 nM and 5.0 nM, respectively, and did not change between day 3 and day 7 after birth. KD for [3H]DAMGO binding was constant (1.1nM), however Bmax increased from 62.2 to 88.3 fmol/mg protein between days 3 and 7 (P < 0.01). This 42% increase in mu receptors may play a role in the increased potency of M6G respiratory effects for guinea pigs during the first week after birth.