We investigated psychobiological substrates of pathological gambling by measuring levels of norepinephrine, monoamine metabolites, and peptides in cerebrospinal fluid, plasma, and urine. Pathological gamblers had a significantly higher centrally produced fraction of cerebrospinal fluid levels of 3-methoxy-4-hydroxyphenylglycol as well as significantly greater urinary outputs of norepinephrine than controls. These results suggest that pathological gamblers may have a functional disturbance of the noradrenergic system. This system has been postulated to underlie sensation-seeking behaviors, aspects of which are thought to be abnormal among pathological gamblers.