The authors investigated the presence of a serum activity inhibiting the specific binding of 3H-flunitrazepam (which labels the central benzodiazepine receptors) (BBIA) in patients with different psychiatric disorders and analyzed it by means of high performance liquid chromatography (HPLC) analysis. The results showed that the lowest activity was present in healthy controls who were not different from patients with schizophrenia and obsessive-compulsive disorder. On the contrary, the BBIA values of these 3 groups of patients were significantly lower than those found in patients with bipolar disorder in various phases (depressive, mixed or manic), in unipolar depressives and in patients with panic and delusional disorders. The HPLC analysis of the serum extracts revealed the presence of 3 peaks of activity which were differently distributed in the patients and in the healthy controls, peak 3 being totally absent in the last group and mainly represented in bipolar depressives. The GABA ratio values showed that peaks 1 and 2 behave as agonists while peak 3 behaves as an inverse agonist. The mass fragmentography of the different peaks is in progress.