Various amphipathic compounds have been found to activate mechanosensitive (MS) ion channels in the bacterium Escherichia coli. These results were interpreted qualitatively in terms of the bilayer couple hypothesis. Here we present a mathematical model that describes the results quantitatively. According to the model, the uneven partitioning of amphipaths between the monolayers of the cell membrane causes one monolayer to be compressed and the other expanded. Because the open probability (Po) of the E. coli channels increased independently of which monolayer the amphipaths partitioned into, the model suggests that Po of the MS channels is determined by the monolayer having higher tension. We derived a relation between Po and amphipath concentration. The kinetics of Po variation after exposure of the cell membrane to the amphipaths was calculated based on this relation. The results fit satisfactorily the experimental data obtained with the cationic amphipath chlorpromazine and with the anionic amphipath trinitrophenol. Experiments which should further test the predictions following from the model are discussed.