In mammalian cells the earliest cellular responses to epidermal growth factor (EGF) have been extensively characterized and include a number of ionic changes, such as a transient increase in calcium influx and a membrane hyperpolarization. The physiological significance of these ionic changes is uncertain. Therefore it is important to establish whether such ionic changes have been conserved during evolution, as this would point to an indispensable role for ionic signaling in growth factor action. We have isolated several embryonic zebrafish cell lines and studied the ionic events elicited by application of EGF to these cells. Using whole cell patch clamp recording, we show that activation of these receptors induces an outward current, which is dependent on the influx of extracellular calcium. The EGF-induced transmembrane currents were abolished by preincubation with different inhibitors of leukotriene synthesis, a feature of EGF-provoked ionic signaling which is also observed in mammalian cell lines. Therefore, these results demonstrate that ionic signaling, as well as the underlying second-messenger systems, is not restricted to mammalian cells, indicating that ionic signaling is of importance in growth factor action.