(1) The effect of calcium, barium and manganese on membrane conductance and spike activity of intestinal smooth muscle, and their influence on the action of adrenaline, was studied. (2) The hyperpolarization and stabilization of the membrane by exposure to excess Ca was associated with a decrease of membrane resistance. Reduction of the external Ca increased membrane resistance. However, with further reduction to zero Ca the membrane resistance became very low; the membrane was depolarized and spike activity was abolished. (3) The addition of Ba (0$\cdot $25 to 1$\cdot $0 mM) to Ca-free medium caused repolarization of the membrane with an increase in membrane resistance and recovery of spike activity. The spike amplitude was increased by about 25 mV per tenfold increase in the external Ba concentration. (4) Higher Ba concentrations (1$\cdot $0 to 2$\cdot $5 mM) prolonged the spike duration resulting in plateau formation and, finally, in a state of sustained depolarization. This could be terminated either by inward current application or by the addition of Ca which restored spikes. As the external Ca concentration was increased the Ba-effect became less, indicating a competition between Ca and Ba. (5) In the presence of Ca, 0$\cdot $5 mM Mn abolished spontaneous spike discharge and 2$\cdot $5 mM Mn also abolished evoked spikes. In Ca-free solution, addition of Mn caused repolarization of the membrane with recovery of membrane resistance, but spike activity remained absent. (6) The action of adrenaline was potentiated by excess Ca and decreased by lowering the external Ca concentration. (7) Adrenaline had no effect when Ca had been substituted by Ba. Traces of Ca restored the action of adrenaline. (8) Mn abolished the action of adrenaline which was not restored by adding Ca. (9) The observations support the view that Ca is important for controlling membrane conductance, that the spike in taenia coli is due to Ca-entry and that Ca is essential for the action of adrenaline. Mn can replace Ca for membrane stabilization, it cannot replace Ca for the spike nor for the adrenaline action. Ba can, to some extent, replace Ca for membrane stabilization and Ba is effective in producing the spike, but Ba cannot replace Ca for the action of adrenaline.