Temporal changes in membrane permeability to bupivacaine (B), etidocaine (E) and mepivacaine (M) documented by their erythrocytic penetration were studied in mice. Temporal variations of B, E and M erythrocytic penetration were demonstrated with a maximum at 04.00 h for B (amplitude = 148%), 10.00 h for E (amplitude = 146%) and at 10.00 h for M (amplitude = 75%). Differences in the circadian pattern of erythrocytic penetration of B, E and M are discussed according to physicochemical properties of these three agents.