Current methods and approaches for the use of HLA markers in the assessment of rheumatoid arthritis (RA) are not optimal. Improved strategies for application of HLA susceptibility genetic typing in patients were evaluated and a new system for rapid determination of these RA susceptibility alleles was developed. Retrospective data summarizing the prevalence of HLA susceptibility alleles in patients with distinct clinical outcomes was analyzed to estimate the sensitivity and specificity of HLA genetic testing as a prognostic marker for erosive disease. A rapid allele specific DNA hybridization assay was performed on an automated instrument using a solid phase nonradioactive hybridization and detection system. Depending on the patient population being tested, from 70-80 percent of patients with progressive erosive disease carry one or more of the DR4 cluster of RA susceptibility genes (DRB1*0401, 0404, 0405). Sensitivity is increased by including other shared epitope positive alleles, but at the expense of specificity. The rapid automated genetic testing system correctly identified each of more than 200 samples tested, with no false positives. HLA genetic testing for RA susceptibility alleles can be performed rapidly and accurately. Prognosis for erosive disease can be facilitated in the patient with early pre-erosive RA using HLA testing in combination with other clinical assessment variables.