Controlled quantities of 100 mM aqueous CaCl₂ solutions were pressure injected into voltage-clamped neurons with a resolution of 10^–11 1. Ca²⁺-selective microelectrodes monitored the time course of changes in [Ca²⁺]_i. At a membrane potential of –50 mV CaCl₂ quantities in the range of 1% of the cell volume induced an inward current, associated with a conductance increase and having an equilibrium potential between –20 and +20 mV, which accompanied the rise in [Ca²⁺]_i. An artifactual origin of the inward current by the injection procedure or by calcium screening of membrane sites could be excluded. The calcium-induced hyperpolarizing conductance, producing an outward current at –50 mV, followed the inward current and reached maximum during the late decline in [Ca²⁺]_i. In most cases its development was separated from the inward current by an intermediate relative decrease of the membrane conductance. Neither of the two transient conductance increases showed a particular dependence on voltage. Renewed Ca²⁺ injection quickly decreased the calcium-induced hyperpolarizing conductance for several seconds. Ca²⁺ injections below 0.05% of the cell volume mostly produced pure outward currents or hyperpolarizing responses. Partial substitution of extracellular CaCl₂ by NiCl₂ decreased the hyperpolarizing response but not the initial inward current. The immediate effects of increased [Ca²⁺]_i are activation of a depolarizing conductance and the partial block of the late hyperpolarizing conductance. The latter is probably produced through intermediate steps after increasing [Ca²⁺ _i.