The frequency of HLA-A, -B, and -DR alloantigens was studied in 46 patients with primary Sjögren's syndrome (pSS), 14 patients with secondary Sjögren's syndrome (sSS) and rheumatoid arthritis (RA), 26 classical RA patients without clinical or histologic evidence of Sjögren's syndrome (SS) and 172 normal controls. A statistically significant increase in the frequency of HLA-DR5 alloantigen was observed in the pSS patients, compared with the controls (P less than 0.007, corrected). No differences were detected between pSS patients with or without extraglandular manifestations, nor were any found between anti-Ro(SSA) positive and negative patients. The frequency of HLA-DR3 alloantigen (30%) was not significantly higher in our pSS population than in controls (25%), nor was that of -DR4 in the RA or the sSS patients. The results of the present study indicate that the 'SS susceptibility gene' in Greek patients is linked with the HLA-DR5 expression gene and they support the hypothesis that the fundamental pSS gene may belong to another locus.