1. Chlorpromazine (CPZ)-induced red blood cell (RBC) swelling was investigated by determination of electrolyte, mean cell volume (MCV) and water content changes in CPZ-treated cells. 2. CPZ-induced RBC swelling is dose-, hematocrit- and pH-dependent, and is associated with a net increase in RBC monovalent cation and Cl- contents. 3. The partition coefficient (Kp) for the CPZ-RBC membrane interaction is pH dependent (Kp = 2500 at pH 7.8; Kp = 840 at pH 6.8). 4. Despite the pH dependence of Kp values an equal number of CPZ molecules is required to induce a 12% increase in MCV at pH 7.8 and 6.8.