To elucidate the influence of total sleep deprivation (TSD) on catecholaminergic neurotransmission, which is assumed to be disturbed in depression, 9 depressive patients collected consecutive 24-h urine samples prior to (baseline), during (TSD) and following total sleep deprivation (post-TSD). Urine samples were analysed for total MHPG (3-methoxy-4-hydroxyphenylglycol), conjugates of MHPG (glucuronide and sulfate), excretion of HVA (homovanillic acid) and VMA (3-methoxy-4-hydroxymandelic acid). TSD increased the urinary excretion of MHPG-sulfate as a marker of the central norepinephrine metabolism and the excretion rates of VMA and HVA as indices of the peripheral catecholamine metabolism. Patients with higher VMA values prior to TSD reacted worse, and the VMA increase due to TSD was positively correlated with the response. The results demonstrate that TSD, besides acting as a stimulus on the peripheral sympathetic nervous system, influences central nervous noradrenergic neurotransmission, as reflected by the increase of MHPG-sulfate.