In isolated papilary muscles of cats and guinea pigs, the inhibitory effect of Ni ions on the slow inward current ( I si) and on the I si-medicated action potential (elicited after inactivation of the excitatory fast Na system of the membrane) was studied. 1. (1) Ni (1 m m) reduced the maximum I si by about 50% and shifted the iv-relationship to weaker currents but left the time-course of I si virtually unchanged. 2. (2) The maximum si-tail current declined to about 50% of the initial control value. τ decay of the tail current being in the range between 35 ms and 50 ms was not altered by Ni ions. The voltage dependence of the steady-state activation ( d∞) remained virtually constant and there was no shift of the d∞-curve along the voltage axis in presence of Ni. 3. (3) According to the decrease of g si , 1 m m Ni reduced both overshoot and V ̇ max of the I si-mediated action potential, and 2 m m Ni induced a blockade of the I si-mediated action potential. The inhibitory Ni effect is Ca dependent and became the weaker the higher the external Ca concentration was, indicating an interaction of Ni with Ca ions. The latter was proved to be of competitive type. Furthermore, in presence of Ni, the I si-mediated action potential behaves no longer as a Ca electrode. 4. (4) In presence of 2 m m Ni, the promoting action of catecholamines on both overshoot and V ̇ max of the I si-mediated action potential depends strictly on the external Ca concentration. It never appeared at Ca concentration lower than 4 m m and was the more pronounced the higher the Ca concentration was.