Arginine vasopressin (AVP) exerts a potentiating effect on the responses of cortisol and ACTH to ovine CRF (oCRF). A stimulation test using AVP plus oCRF to assess ACTH reserve has been proposed. In central diabetes insipidus, long-term substitution therapy is commonly undertaken with desmopressin (DDAVP), an analogue of the natural hormone which has a greater antidiuretic action but whose effects on the ACTH-cortisol axis are still controversial. The aim of our study was to evaluate the variations in the responses of ACTH and cortisol to oCRF in various phases of the treatment of central diabetes insipidus: no treatment, endonasal treatment with DDAVP solution and oral treatment with DDAVP in tablet form. Seven patients suffering from central diabetes insipidus underwent testing with oCRF during the various phases of treatment. In the absence of DDAVP treatment, normal responses were registered for cortisol (basal 164.1 +/- 29.4 ng ml-1, peak 396.1 +/- 37.9 ng ml-1; P < 0.05) and ACTH (basal 20.4 +/- 3.9 pg ml-1, peak 86.3 +/- 20.9 pg ml-1; P < 0.05) in all patients. During oral treatment with DDAVP, no variation in cortisol response to oCRF was seen. By contrast, when DDAVP was administered endonasally, a significant reduction in cortisol responsiveness to oCRF (secretory area: 2429 +/- 548 ng ml-1 120 min) was noted in comparison with that found during the other two tests (no treatment: 3070 +/- 704 ng ml-1 120 min; oral DDAVP: 3419 +/- 650 ng ml-1 120 min; P < 0.05) performed.(ABSTRACT TRUNCATED AT 250 WORDS)