One target of autoantibodies in sera of patients with systemic lupus erythematosus or primary Sjögren's syndrome is the nuclear autoantigen La/SS-B. Lambda clones and cosmids were isolated, which contained the sequences of the La gene and the three La pseudogenes. They were used for preparation of a physical map. Finally, the La gene and pseudogenes were sequenced. The pseudogenes were characterized as retropseudogenes. Their evolutionary ages were estimated to be approx. 4, 4.5 and 5 million years. Inserts of 4, 16 and 24 nucleotides, which were mostly A-residues, were found in exon 7 of the respective pseudogene. The oldest pseudogene contained the longest insert, the youngest pseudogene contained the smallest insert. The oligonucleotides seem to be the result of repeated inserts of A-residues in a hot spot region of the La genes. Two La cDNAs were isolated which contained either a deletion or an insert of an A-residue at the same position.