Insulin-like growth factor II (IGF II) is a member of somatomedin family and is a potent mitogen in various types of mammalian cells. We have recently reported that IGF II stimulates calcium influx in competent BALB/c 3T3 cells primed with epidermal growth factor (J. Biol. Chem. 262: 12120-12126, 1987). Using patch-clamp technique, we show here an IGF II-sensitive cation channel in BALB/c 3T3 cell plasma membrane. Calcium is permeable to this cation channel and its opening behavior is independent of membrane potential. IGF II increases the opening probability of the identical channel in cells pretreated sequentially with platelet-derived growth factor and epidermal growth factor, whereas IGF II does not affect the opening of the channel in G0-arrested cells. This cation channel activity is observed only when IGF II is included in the patch pipette, indicating direct regulation of the channel by IGF II. We suggest that IGF II stimulates calcium influx by opening this cation channel and that IGF II activates the channel in a unique cell cycle-dependent manner.