Family studies suggest an interrelationship between Gilles de la Tourette Syndrome (GTS) and some forms of obsessive-compulsive disorder (OCD). Some authors consider GTS to be part of a serotonergically mediated cluster of OCD spectrum disorders. The present study was undertaken to compare measures of psychopathology, personality and blood serotonin between GTS and OCD (without ties), and to investigate whether an OCD spectrum hypothesis is supported for GTS. Fifteen GTS without OCD subjects, 21 tic with (+) OCD subjects, 15 OCD without tie subjects and 26 controls tall without serotonergic medication) were evaluated with self-rated and clinician-rated measures of psychopathology and personality. Whole blood serotonin (5-HT) and platelet monoamine oxidase activity (MAO) was measured, and Spearman's correlations were calculated between whole blood 5-MT, MAO and rating scale scores within the entire sample and within subgroups. There were main effects of OCD on anxiety, obsessive-compulsive, neuroticism and extraversion scores. There were main effects of ties on depression, obsessive-compulsive, trait anxiety and neuroticism scores, and on platelet MAO. There were interaction effects on platelet MAO, 5-MT, Yale-Brown Obsessive-Compulsive Rating Scale severity, trait anxiety and Eysenck Personality Questionnaire neuroticism scores. Platelet MAO activity was elevated in tie-free OCD subjects when compared to tie + OCD, GTS without OCD and controls. Whole blood 5-HT was lowered in tie + OCD patients in comparison to GTS without OCD and tie-free OCD subjects. Whole blood 5-HT and obsessive-compulsive severity were negatively correlated within OCD without tie patients and MAO and Leyton Obsessive Inventory scores were negatively related within GTS without OCD patients. The biochemical data of this study suggest that in tie + OCD and in tie-free OCD patients, 5-HT dysregulations play a role, but not necessarily in pure GTS. Serotonergic dysregulations within tie c OCD and tie-free OCD patients are distinct, suggesting differences in underlying pathophysiology. The finding that obsessions and compulsions can be associated with either 5-HT hypofunctionality or hyperfunctionality reveals a major weakness in the OCD spectrum theory, i.e. that the associations between obsessive-compulsive behaviours and 5-HT abnormalities are less specific than suggested by the original obsessive-compulsive spectrum model.