Anti-La antibodies usually occur in sera with anti-Ro antibodies and represent important serologic markers of Sjögren's syndrome and neonatal lupus erythematosus. In addition to their diagnostic and prognostic significance, anti-La antibodies have proved valuable reagents for molecularly characterizing its antigenic target, which is a 47 kD ribonucleoprotein located in the nucleus and cytoplasm of mammalian cells. The isotype distribution and fine specificity of the anti-La response as well as its associations with HLA-DR and DQ loci suggest that these autoantibodies arise by a T cell-dependent, antigen-driven mechanism. Further insights into the mechanisms of anti-La production in humans may be gained by studying experimental animal models that develop these antibodies spontaneously or through induction by various immunization protocols.