Data reported in this communication suggest that, despite severe manic behavior, morning plasma cortisol concentration was normal and 24 hour urinary excretion of 17-OHCS was high normal in nine manic depressive patients. Evening plasma cortisol concentration was also within normal range despite being significantly higher than during recovery. This diminishes the amplitude of the diurnal fall in cortisol concentration but does not result in absolute loss of circadian rhythm of cortisol. The possibility of mania as a defense and its interaction with the pituitary-adrenal axis is discussed, along with the possibly decreased effectiveness of this defense during the latter part of the patients' waking day.