Abstract Role of surface activity in the mechanism of action of thioridazine (THR) has been studied. THR has been shown to generate liquid membrane it self and also in association with the relevant membrane lipids, sphingomyelin and cholesterol in series with a supporting membrane. Transport of relevant biogenic amines e.g. dopamine, nor-adrenaline, adrenaline, serotonin, gamma amino butyric acid (GABA) and glutamic acid and ions viz. sodium, potassium, and calcium has been studied in the presence of liquid membranes generated by THR and THE in association with sphingomyelin–cholesterol. The data on modifications in the permeability of relevant biogenic amines and ions indicate that the liquid membranes generated by THR may contribute to the mechanism of action of THR.