<i>Background:</i> Plasma prolactin levels are sensitive to dopamine and serotonin function, and fatigue. Low cortisol, dopamine and/or serotonin may be involved in burnout and detachment. <i>Methods:</i> In this double-blind within-subject study, we treated 9 female burnout subjects and 9 controls with 35 mg cortisol and placebo orally. We measured state affect and plasma prolactin, oxytocin, cortisol and adrenocorticotropic hormone levels, and administered an attachment questionnaire. <i>Results:</i> The burnout subjects displayed an extreme distribution of basal prolactin levels, displaying higher or lower levels compared to the controls. The low prolactin burnouts had profoundly low attachment scores and tended to have low oxytocin levels. The high prolactin burnout subjects tended to show cortisol-induced decreased prolactin and fatigue, and increased vigor. <i>Conclusion:</i> Results are consistent with the hypothesis that burnout subjects are either characterized by low serotonergic function or by low dopaminergic function, and that the latter group benefits from cortisol replacement. These preliminary results suggest that differentiating between two syndromes may resolve inconsistencies in research on burnout, and be necessary for selecting the right treatment strategy.