Due to their high information content and their particular mode of variation, large rRNA molecules potentially represent powerful indicators of phylogenetic relationships. Even partial sequences may suffice to generate reliable estimations, provided they correspond to well-chosen portions of the molecule. We have systematically analyzed a specific portion of the large rRNA (the region extending over nearly 400 nucleotides from the 5′ end) as a general index of eucaryotic phylogeny. By means of fast and direct rRNA sequencing, we have determined the sequence of this region for 20 additional eucaryotes, including several representatives of each vertebrate class, an invertebrate metazoan (mussel), a fungus (Schizosaccharomyces pombe), and three higher plants. Comparative treatment of these new data and previously reported rRNA sequences shows that this region can serve as an indicator of eucaryotic phylogeny for evaluating both long-range and short-range relationships. Its conservative domains appear to possess a rather uniform rate of nucleotide changes in all the eucaryotic lineages analyzed and the phylogenetic tree we derived agrees with classical views.