Autoantibodies to La/SSB are found in sera of patients with primary Sjogren's Syndrome (pSS) and Systemic Lupus Erythematosus (SLE). A large body of these autoantibodies are directed towards discrete linear epitopes comprising the sequences 289-308 aa and 349-364 aa. Several previous studies have shown that in the sequence 289-308 aa resides also a T-cell epitope. Based on "molecular recognition" theory, complementary peptides cpep289-308 and cpep349-364, derived by anti-parallel readings of the non-coding strand of La/SSB DNA encoding epitopes 289-308 and 349-364 respectivelly, were synthesized. Complementary peptides cpep289-308 and cpep349-364 presented inverted hydrophobicity profiles, compared with sense peptides and recognized by 28% and 51% of anti-La/SSB positive sera respectively. F(ab')2 fragments were prepared after pepsin enzymatic degradation of affinity purified anti-pep and anti-cpep specific IgG. Anti-pep IgG found to specific recognize anti-cpep F(ab')2 fragment and vice versa, suggesting an idiotype - antiidiotype relation. Homologous inhibition with soluble anti-pep or anti-cpep F(ab')2 further confirmed this relation. In addition soluble pep, cpep or recombinant La/SSB inhibited (65%-85%) anti-pep and anti-cpep interaction indicating that the idiotype is located within the antigen binding site of anti-La/SSB antibodies. Anti-pep349-364 antibodies, purified from different patient sera were all found to recognize the same anti-cpep F(ab')2 suggesting that a common idiotype exists. Immunizations of BALB-c non-autoimmune mice with pep289-308 produced anti-pep289-308 followed by the production of anti-cpep289-308 antibodies 10 days later. In a similar manner immunization with cpep289-308 led to the appearance of anti-cpep289-308 followed by the formation of anti-pep289-308 antibodies. In conclusion, antibodies to B-cell epitopes of La/SSB contain in their antigen binding site a common idiotype which can be detected using complementary peptides to these epitopes. Antibodies to La/SSB epitopes are target of an anti-idiotypic response against this common idiotype. Manipulation of this Id - anti-Id network may provide potential insights into the understanding of the molecular mechanisms for autoantibody production and therapeutic approaches.