This study examined the integrity of hypothalamic-pituitary-adrenal (HPA) axis in clomipramine model of depression. Male rat pups were treated twice daily from postnatal day 5 to 21 with clomipramine (15 mg/kg, s.c.). At three months of age, serum corticosterone level was estimated before and after dexamethasone (100 microg/kg, s.c.) administration and after subjected to REM sleep deprivation (RSD) for 4 days consecutively. Data indicated enhanced baseline corticosterone levels and nonsuppression to dexamethasone in clomipramine treated rats. The corticosterone levels however, reversed to the levels of control group in rats subjected to RSD. These findings thus indicated for the first time an HPA hyperactivity in rats treated with clomipramine during neonatal period and are in harmony with cholinergic hypersensitivity reported earlier in this model of depression.