Twenty-three patients (5 to 15 years of age) with primary nocturnal enuresis were treated with desmopressin (DDAVP) according to a four-step protocol with weekly reductions of daily doses (1 to 0.25 microgram/kg body weight) thus including aspects of behavior-oriented "bladder retention training". The rate of wet nights was significantly reduced while patients were on medication (p < 0.02), but the sample as a whole returned to baseline levels after medication was stopped. Six subjects (26%) were non-responders. A variety of psychological and psychosocial single factors did not significantly affect the outcome. However, a subgroup of seven patients assessed as "psychologically non-distressed" revealed better results both on medication (p < 0.02; reduction 73%) and off medication (p > or = 0.05; reduction 39%) compared to a "distressed" subgroup (N = 16). Both groups showed significant changes in wet nights over the treatment course (p < 0.02 and p > or = 0.002, respectively). There was no clear-cut relationship between laboratory data (urine volume, osmolality, vasopressin) and outcome in wet nights. Data did not suggest a subgroup of patients with particularly low nocturnal vasopressin (AVP) secretion and, thus, high rates of wet nights. Our results corroborated the finding that DDAVP is an effective substance in reducing wet nights in patients with primary nocturnal enuresis. However, with respect to major reductions and long-term results (off medication), these preliminary findings suggest that "psychological distress" seems to be a very important confounding outcome variable. Thus, careful consideration and assessment of psychological and psychosocial aspects of distress are recommended. Eventually, a combination of DDAVP treatment with counseling and/or psychotherapy may significantly improve results for the majority of patients and families.