Oligodeoxyribonucleotides complementary to the initiation region of rabbit beta-globin messenger RNA were used to selectively inhibit translation in a wheat germ extract and in injected Xenopus oocytes. The oligonucleotides interacted specifically with their RNA target as shown by thermal denaturation studies of hybrids on nitrocellulose filters. The longest oligonucleotide used (17-mer) efficiently blocked translation both in vitro and in vivo. In contrast the shortest one (8-mer) exhibited only a limited effect. The translation block was specific. The synthesis of endogenous proteins in oocytes and that of alpha-globin in the in vitro system were not affected by anti-beta-globin oligonucleotides. A non-complementary oligonucleotide had no inhibitory effect.