Increased tolerance to noxious stimuli during pregnancy has been demonstrated. The purpose of this study was to examine the effect of SCH 32615, an inhibitor of one of the enzymes (enkephalinase) responsible for the degradation of endogenous enkephalins, on pregnancy-induced analgesia in mice. Analgesia was tested using the hot-plate and tail-flick tests. For the hot-plate test, animals were tested in late pregnancy (Day 17 or Day 18 of pregnancy; mice deliver on Day 19) and in the postpartum period (Days 2 and 8 after delivery) in the following groups: i) no treatment (n = 15); ii) vehicle only (n = 15); iii) SCH 32615 250 mg/kg (n = 20), 150 mg/kg (n = 15), 50 mg/kg (n = 14); iv) naloxone 5 mg/kg (n = 15); v) naloxone 5 mg/kg+SCH 32615 150 mg/kg (n = 10); vi) nonpregnant control given SCH 32615 150 mg/kg (n = 14). All drugs were given subcutaneously. Hot-plate latency (HPL) was significantly higher in pregnant mice (mean hot-plate latency 17.5 s) than postpartum mice (mean hot-plate latency 11 s on Day 2 and 8.5 s on Day 8). SCH 32615 250 mg/kg and 150 mg/kg significantly enhanced this analgesia in pregnant mice (mean percent of maximum possible effect 24.2 and 29.9, respectively) but not SCH 32615 50 mg/kg or the vehicle alone (mean percent of maximum possible effect 12.4 and 0.5, respectively). Naloxone significantly lowered HPL in pregnant mice (19.8 s-16.2 s) and antagonized the effect of SCH 32615.(ABSTRACT TRUNCATED AT 250 WORDS)