We identified four cDNA sequences encoding sheep homologues of the CD1 molecule. The sheep sequences were selected from lambda gt11 thymocyte cDNA libraries by hybridization with a human CD1C probe and a homologous sheep probe. The SCD1B-42 and SCD1A25 sequences encode complete CD1 molecules. The third sequence, SCD1B-52, which is closely related to SCD1B-42 and may be an allele, has the sequence encoding the alpha 3 region precisely deleted. The fourth sequence, SCD1T10, is truncated at the 5' end. All four sequences are related to the human CD1B and domestic rabbit CD1B-like sequences at both nucleotide and amino acid level. Comparison of the derived CD1 amino acid sequences with the sequence of major histocompatibility complex class I molecules showed that the sheep CD1 molecules, like human CD1 molecules, lack most of the conserved class I residues known to be involved in interaction with beta(2)-microglobulin and the CD8 molecule. They do not contain the peptide docking residues involved in anchoring peptides in the peptide binding groove of class I molecules. Southern hybridization of sheep DNA with a sheep CD1 exon 4/alpha 3 probe showed that the sheep genome encodes at least seven CD1 genes. The implications of these analyses for CD1 function are discussed.