The distribution of HLA-DP antigens were studied in 41 patients with alopecia areata (AA) and 188 ethnically matched controls. An increase of DR4 and possibly DR5 in 24 of these patients has previously been reported. HLA-DP typing for DPw1 through w6 and the local specificity, CDP HEI, was performed using the primed lymphocyte typing (PLT) technique. The frequencies of DPw4 were 92.9% in AA patients and 71.3% in controls (relative risk, RR = 5.1, p = 0.0019 and p less than 0.03 when corrected). DPw1 was decreased to 4.9% in patients compared to 14.9% in controls, but the difference was not statistically significant. The frequency of DR4 was 48.8% compared to 31.9% in controls (RR = 2.0) whereas the frequency of DR5 did not differ from that in controls. DPw4 was not associated (in linkage disequilibrium) with DR4 or DR5 in patients or controls. Thus, in AA the association with DP and DR are independent of each other. However, individuals with both the DPw4 and DR4 alleles are at increased risk for AA, indicating that synergism between DP and DR gene products may play a role in the genetic susceptibility to AA.