We used an oligonucleotide probe specific for a polymorphic sequence in the HLA-DQ beta gene to investigate the role of DQ polymorphism in genetic susceptibility to Felty's syndrome (FS) and rheumatoid arthritis (RA). The sequence of this gene was identified from a complementary DNA library derived from an RA patient's B lymphoblastoid cell line. With this probe, we studied the prevalence of the specific DQ beta allele in DR4 positive FS patients, RA patients, and normal control subjects. Significantly more FS patients (17 of 25) showed hybridization with this oligonucleotide probe, compared with the number of DR4 positive non-FS RA patients (7 of 23) and normal controls (7 of 21). The findings indicate that genes linked to the DQ region are important in determining susceptibility to FS.