Krüppel (Kr), a segmentation gene of Drosophila, encodes a protein sharing structural features of the DNA-binding "finger motif" of TFIIIA, a Xenopus transcription factor. Low-stringency hybridization of the Kr finger coding sequence revealed multiple copies of homologous DNA sequences in the genomes of Drosophila and other eukaryotes. Molecular analysis of one Kr-homologous DNA clone identified a developmentally regulated gene. Its product, a finger protein, relates to Kr by the invariant positioning of crucial amino acid residues within the finger repeats and by a stretch of seven amino acids connecting the finger loops, the "H/C link." This H/C link is conserved in several nuclear and chromosome-associated proteins of Drosophila and other eukaryotic organisms including mammals. Our results demonstrate a new subfamily of evolutionarily conserved nuclear and possibly DNA-binding proteins that again relate to a Drosophila segmentation gene as in the case of the homeo domain.