GLUCOCORTICOIDS, in conjunction with their cognate receptors, exert negative-feedback effects on the hypothalamus-pituitary-adrenal axis, suppressing adrenal steroid secretions. Two types of corticosteroid receptor, distinguishable by their ability to bind corticosterone, have been identified as classical mineralocorticoid (type I)¹ and glucocorticoid (type II)² receptors by cloning their complementary DNAs. The type I receptor controls the basal circadian rbvthm of corticosteroid secretion. Both receptor types are involved in negative feedback³, but the type II receptor may be more important for terminating the stress response as it is the only one to be increased in animals rendered more sensitive to corticosteroid negative-feedback effects⁴. Here we create a trans-genic mouse with impaired corticosteroid-receptor function by partially knocking out gene expression with type II glucocorticoid receptor antisense RNA. We use this animal to study the glucocor-ticoid feedback effect on the hypothalamus-pituitary–adrenal axis.