This project evaluated a wide variety of factors which contribute to the urinary excretion of 3-methoxy-4-hydroxyphenyl glycol (MHPG), the norepinephrine metabolite thought best to reflect brain turnover. Major findings are as follows: (1) MHPG excretion is influenced by a variety of factors such as stress, diet and physical activity, but the effects are different in normal controls compared to depressed patients. This observation raises an important methodological question concerning the usefulness of normal subjects as controls for the contribution of these variables to amine metabolite changes in depressed patients, and suggests that defective "buffering" systems for the regulation of norepinephrine turnover may be important in affective illness; (2) urinary MHPG shows a clear diurnal pattern in normal controls but not in depressed patients; (3) in both patients and controls, there is a positive correlation between urinary MHPG and blood pressure; (4) longitudinal studies in cyclic manic-depressive patients indicate that, in the same patient, greater amounts of this metabolite are excreted in the manic phase than in the depressive phase. However, these alterations in MHPG follow an arrhythemic pattern of fluctuation, somewhat out of phase with the mood cycle itself.