Imipramine (IP) is an amphiphilic amine that is clinically useful as a tricyclic antidepressant. In the present work, we have investigated the pH effects on (a) the micellization properties of IP, (b) IP-induced release of aqueous contents from artificial vesicles (liposomes), and (c) IP-induced haemolysis, under hypotonic and isotonic conditions, in the pH range 5.0–10.0. Our data show that IP-membrane interaction caused important membrane destabilisation. However, changes in pH modified strongly the effects of IP. We suggest that the parameters of IP-induced model and cell membrane lysis are sensitive to the changes in the charge of this amphiphile. IP interacts more strongly with the membrane at basic pH (smaller net charge) than at neutral or acidic pH. A simple interpretation of these data is that increasing pH causes a decrease in IP net charge, thus a decrease in the critical micellar concentration of IP, and an increased partition into the lipid bilayer. Concomitantly, pH variations both above and below 7 tend to destabilise the cell membrane, so that the protective effect of IP against hypotonic haemolysis has a maximum at neutral pH.