Fertilization of frog eggs by frog sperm is inhibited if the egg's membrane potential is positive (N.L. Cross and R.P. Elinson, 1980, Dev. Biol. 75, 187-198); however, fertilization of salamander eggs by salamander sperm does not depend on membrane potential (M. Charbonneau, M. Moreau, B. Picheral, J.P. Vilain, and P. Guerrier, 1983, Dev. Biol. 98, 304-318). Since salamander sperm can fertilize frog eggs, we have investigated whether this cross-fertilization is voltage dependent. If, during insemination with Notophthalmus sperm, Xenopus eggs were voltage clamped between +7 and +20 mV, fertilization proceeded in 7/10 (70%) of the clamped eggs, compared to 38/48 (79%) of the neighboring eggs. In control experiments in which voltage-clamped Xenopus eggs were inseminated with Xenopus sperm, fertilization proceeded in only 1/10 (10%) of the clamped eggs, compared to 59/60 (98%) of the neighbors. Similar results were obtained with cross-fertilization experiments between Notophthalmus sperm and Rana eggs. These experiments indicate that the voltage dependence of fertilization depends on the species of sperm.