Autoantibodies in Sjögren's syndrome (SS) were identified by their precipitin reactions with tissue antigens in immunodiffusion. The source of antigens was a sonicated extract of human lymphoid cells (WiI2) grown in tissue culture. Three distinct precipitin systems were identified and referred to as precipitins SS-A and SS-B, and rheumatoid arthritis precipitin. These studies show that precipitins SS-A and SS-B are present in high frequency in sera of patients with SS without associated rheuamtoid arthritis (RA) and are absent or present in low frequency in many other connective tissue diseases. On the other hand patients with SS who also had clinical features compatible with RA (SS-RA) did not have precipitins SS-A and SS-B but had rheumatoid arthritis precipitin (RAP). The latter precipitin was also present in RA patients in a similar order of frequency as in SS-RA. All three precipitin systems were shown to be reactions betweeen immunoglobulins and cellular antigens. The origin of SS-A and SS-B antigens was demonstrated by immunofluorescence to be primarily from the nucleus but the origin of RAP in the cell has not been established.