An endogenous electric field (EF) exists in the vertebrate lens, but the influences of this on the functions of lens epithelial cells (LECs) are unclear. Because LECs from different regions experience different patterns of endogenous EFs and show striking differences in morphology and function, bovine LECs from different regions were cultured in an applied EF to mimic that occurring naturally. The migration of LECs from central and peripheral regions was both stimulated and directed by an applied EF. Field-directed cell migration required serum, or growth factors. Cells cultured in serum free medium lost directed migration completely and this was restored partially by the addition of basic fibroblast growth factor. The direction of cell migration depended on both EF-strength and the origin of the LECs. Both central and peripheral LECs moved anodally at 150-250mVmm(-1). In a low EF (50mVmm(-1)), peripheral LECs migrated in the opposite direction, cathodally, but central LECs did not respond. Peripheral LECs alone therefore showed field strength dependent, bi-directional migration. A physiological EF enhanced activation of ERK1/2, a signaling molecule in the MAP kinase pathway, and this also required serum. Interestingly, expression of active ERK1/2 was enhanced in peripheral LECs at both 50 and 200mVmm(-1), which stimulated migration in different directions. In central LECs, which showed directed migration only at higher EFs, active ERK1/2 was increased only at 200mVmm(-1). The MAP kinase inhibitor U0126 prevented activation of ERK1/2 in LECs and inhibited EF-directed migration, implicating MAP kinase signaling in directing the migration of LECs in a physiological EF.