We have determined the nucleotide sequence of a cloned cDNA derived from the mRNA encoding an abundant Xenopus laevis tadpole beta-globin polypeptide. The cloned sequence contains the entire coding region of the mRNA as well as most of its 5'- and 3' -noncoding regions. The complete amino acid sequence of the protein has been deduced. Comparison of this sequence with that of the major adult beta-globin polypeptide of X. laevis shows that the two gene products are highly diverged from each other, the tadpole sequence actually displaying a somewhat greater homology to the human beta-like globin sequences than to the adult frog sequence. An unusual feature of the predicted tadpole beta-globin polypeptide is the presence of a phenylalanine residue at its carboxyl terminus. All known amphibian, avian, and mammalian beta-globin polypeptides have a COOH-terminal histidine residue, and this amino acid is known to play a major role in the alkaline Bohr effect. This observation suggests that, as has been found for two fish hemoglobins which also have a COOH-terminal phenylalanine residue, the tadpole hemoglobin of X. laevis will display a much reduced alkaline Bohr effect.