We studied plasma vasopressin concentrations during hypertonic saline infusions in 5 men with hypogonadism and 10 normal men to investigate the effect of gonadal steroid on hypothalamo-neurohypophyseal function. All the subjects received the infusion of 5% saline, and plasma vasopressin concentrations were determined by radioimmunoassay (RIA). Three of the 5 men were patients with isolated hypogonadotropic hypogonadism (IHH) and the other wo were patients with Klinefelter's syndrome. None of them had any symptoms of diabetes insipidus. Although there was no difference between basal plasma osmolality in the patients and the normal subjects (287.2±2.1 vs. 285.3±1.8 mmol/kg), the basal level of plasma vasopressin in the patients was lower than that in the normal subjects (0.62±0.17 vs. 1.36±0.15pg/ml, P<0.05). Hypertonic saline infusion revealed varying degrees of subnormal vasopressin responses in the patients except one patient with Klinefelter's syndrome. The mean vasopressin response to osmotic stimuli (Δ plasma vasopressin / Δ plasma osmolality) in the 5 patients was lower than in the normal subjects (0.04±0.01 vs. 0.16±0.02, P<0.05). Three patients with IHH and one patient with Klinefelter's syndrome were re-examined after pulsatile gonadotropin-releasing hormone (GnRH) infusion or testosterone enanthate i.m. injection. After the treatment with testosterone or GnRH, the response of plasma vasopressin to hypertonic saline infusion was normalized in three patients who had subnormal vasopressin response before treatment (Δ plasma vasopressin / Δ plasma osmolality: 0.04±0.01 vs. 0.09±0.01, P<0.05). These results suggest that testosterone improves the subnormal vasopressin response to osmotic stimuli in men with hypogonadism.