IN THIS PAPER the results of an investigation of adrenal cortical activity in manicdepressive illness are reported. Two rapidly cycling manic-depressive patients were studied in the hospital through several cycles by daily clinical assessment of their psychological state, and by daily measurement of 24-hour urinary 17-hydroxycorticosteroid (17-OHCS) excretion. These patients also underwent metabolic turnover studies of radioactive tryptonhan in an attempt to elucidate possible effects of differing levels of adrenal cortical activity on intermediary metabolism of tryptophan. Rapidly cycling manic-depressive patients were chosen for study because changes in adrenal cortical activity have been demonstrated during different phases of the affective cycle. Tryptophan metabolism was studied because the activity of tryptophan pyrrolase, the rate-limiting enzyme in the metabolism of tryptophan to kynurenine, has been demonstrated to be influenced by hydrocortisone. This study was undertaken to further investigate adrenal cortical