Twenty-six unrelated Spanish Caucasian individuals affected by pemphigus vulgaris (PV) were HLA typed and frequencies compared with those of 200 ethnically matched healthy controls. Twenty-three out of 26 patients were HLA-DR4. The frequency of HLA-DR14 was also increased (31%; controls: 4%). Of the 23 patients positive for HLA-DR4, 21 carried the DRB1*0402 allele. Therefore, the frequency of HLA-DRB1*0402 among patients was 81% (4% in controls; P=4.7x10(-27), OR=100.8). Interestingly, HLA-DR13, a frequent HLA-DR specificity in the Spanish general population (27%), was absent among the PV patients (P=0.009; Pc=0.1; OR=0.05). Taking together these data, we can conclude that, in the Spanish population, PV is preferentially and strongly associated with HLA-DRB1*0402, whereas DRB1*13 seems to confer a protective effect in our population.