The isolated Ca2+ current from Paramecium caudatum was examined under voltage clamp with long conditioning depolarizations lasting for up to 5 min. The isolated transient Ca2+ current inactivates with tens of milliseconds due to Ca2+ -dependent Ca2+ -channel inactivation (Brehm & Eckert, 1978). When this fast inactivation was blocked by internally delivered EGTA, a much slower inactivation of the Ca2+ current was discovered. This slow inactivation had time constants of tens of seconds, depending on voltage. The development of this slow inactivation was further examined by following the Ca2+ transient after 1 s interruptions of the long depolarization. This development is voltage dependent; the rate of inactivation is higher with a larger depolarization. After a long depolarization, the Ca2+ current returns in two clearly separable steps. A portion of the current returns rapidly along an exponential time course with time constants of tens to hundreds of milliseconds. The remainder of the current returns slowly with time constants of tens of seconds. A longer conditioning depolarization generates a larger portion that recovers slowly. Internally delivered EGTA, sufficient to prevent most of the fast inactivation, did not change the time course or the extent of either the onset or the removal of the slow inactivation. The compound W-7, which inhibits the Ca2+ current itself, does not block the onset of this slow inactivation during depolarization. We conclude that the slow inactivation of the Ca2+ channel is a mechanistically different phenomenon from the fast Ca2+ -dependent Ca2+ -channel inactivation. The possible physiological and behavioural roles of this slow inactivation are discussed.