Glucocorticoids are known to inhibit the AVP response to osmotic and hemodynamic stimuli in humans. In the present study, we examined whether the AVP response to other primary stimuli, such as insulin-induced hypoglycemia and cigarette smoking was sensitive to inhibition by dexamethasone. The plasma ACTH responses were also measured. Twenty-four normal men were randomly divided into 3 groups of 8 subjects. One group was tested with insulin (0.15 IU/kg in an iv bolus) and another group with cigarette smoking (2 non-filter cigarettes smoked in succession within 10 min) with and without pretreatment with dexamethasone (2 or 4 mg in an iv bolus 10 min before insulin or smoking). The third group was tested with dexamethasone alone (2 or 4 mg in an iv bolus). The administration of dexamethasone (2 or 4 mg) alone did not modify the circulating levels of AVP and ACTH at any time during the next hour. The hypoglycemic response to insulin was similar regardless of dexamethasone treatment. AVP rose sharply in response to both hypoglycemia and smoking, reaching mean peak levels at 45 and 30 min, respectively. After both stimuli, the mean peak levels of AVP were 2.25 times higher than baseline. Pretreatment with dexamethasone (2 or 4 mg) significantly decreased the AVP responses to both hypoglycemia and cigarette smoking. Following pretreatment with dexamethasone (2 or 4 mg) the AVP increments in response to hypoglycemia or cigarette smoking were only 1.7 times higher than baseline. The plasma concentrations of ACTH were strikingly increased by hypoglycemia. The mean peak level was 3.5 times higher than baseline and was reached at 45 min.(ABSTRACT TRUNCATED AT 250 WORDS)