A compositional transition was previously detected by comparing orthologous coding sequences from cold- and warm-blooded vertebrates (see Bernardi, G., Hughes, S., Mouchiroud, D., 1997. The major compositional transitions in the vertebrate genome. J. Mel. Evol.44, S44-S51 for a review). The transition is characterized by higher GC levels (GC is the molar ratio of guanine+cytosine in DNA) and, especially, by higher GC(3) levels (GC(3) is the GC level of third codon positions) in coding sequences from warm-blooded vertebrates. This transition essentially affects GC-rich genes, although the nucleotide substitution rate is of the same order of magnitude in both GC-poor and GC-rich genes. In order to understand the evolutionary basis of the changes, we have compared the hydrophobicity of orthologous proteins from Xenopus and human. Although the differences are small in proteins encoded by coding sequences ranging from 0 to 65% in GC(3), they are large in the proteins encoded by sequences characterized by GC(3) values higher than 65%. The latter proteins are more hydrophobic in human than in Xenopus. (C) 1999 Elsevier Science B.V. All rights reserved.