The response to 1-deamino-8-D-arginine vasopressin (DDAVP), an intranasally administered analogue of vasopressin, was investigated in children and adults with central diabetes insipidus. To assess the action of DDAVP on the distal nephron, cyclic adenosine monophosphate (cAMP) excretion was assayed in urine collected 4 hr before and during four subsequent 4-hr periods after intranasal administration of 5 micrograms DDAVP. Maximal effects on urine volume and concentration were observed between 4 and 12 hr, coinciding with an elevated cAMP excretion in seven subjects. The pretreatment 4-hr cAMP excretion (micrograms/gm creatinine) correlated inversely with age (p less than 0.02) and surface area (p less than 0.001). Subsequent cAMP excretion after DDAVP increased inconsistently with no relationship to duration of antidiuresis, indicating that urinary cAMP is a poor index of antidiuretic hormone action on the distal nephron. We also confirmed that DDAVP intranasally induces antidiuresis in patients with diabetes insipidus over approximately 12 hr.