Ionic currents were recorded from Xenopus oocytes injected with RNA isolated from chick or mouse brain. Three currents were studied: a rapid tetrodotoxin-sensitive Na+ current (INa), an early outward K+ current sensitive to 4-aminopyridine (IA), and an inward current activated by the excitatory amino acid receptor agonist kainate. Oligonucleotides (60-80 bases long complementary to rat brain Na+ channel sequences were prehybridized to chick brain RNA. These DNA sequences, upon injection into oocytes, specifically inhibited expression of IN, relative to IA and the kainate-induced current in a dose-dependent manner. By contrast, prehybridization of oligonucleotides complementary to sequences either from the Drosophila Shaker locus (which codes for an early K+ current in Drosophila muscle) or from a homologous clone from mouse brain did not block the expression of the early outward K+ current induced in the oocytes by mRNA from chick or mouse brain. This method provides a convenient means for testing the functional role of cloned DNA species.