Trazodone is a novel antidepressant drug with alpha-adrenolytic activity. Since alpha 1-adrenoceptor mechanisms have been shown to stimulate basal cortisol secretion in healthy humans, the neuroendocrine effects of trazodone (75 mg orally) were evaluated in six healthy subjects. The drug plasma levels were also measured. With respect to placebo, trazodone significantly decreased plasma cortisol concentrations (F = 9.173, p less than 0.01). The areas under the curve (AUC) of plasma trazodone concentrations were negatively correlated with the AUC of plasma cortisol levels (r = -0.95, p less than 0.0005). These results confirm that, in humans, alpha 1-adrenergic mechanisms stimulate the basal secretion of cortisol.