In the present study we have investigated the HLA-B8,DR3-associated control of serum IgA levels in 110 randomly selected HLA-typed healthy subjects. Serum IgG, IgA, IgM and IgE levels were measured in all individuals. The values were analyzed according to age, sex and HLA-DR phenotype. No correlation between age and serum IgA, IgM and IgE levels was found in our homogeneous sample, since all subjects studied were in a narrow age range, i.e. 20-49 years. In contrast, a significant positive correlation was found for IgG levels. The mean IgM level was significantly higher in females than in males, whereas the mean IgA and IgE levels were significantly lower in females. HLA-DR2-positive subjects displayed the significantly highest levels of serum IgE, whereas HLA-B8,DR3-positive subjects showed the significantly lowest levels of serum IgA. Thus, our results show that in our random sample sex and DR phenotype are involved in the control of serum IgA, IgM and IgE levels. The genetic control of sex and HLA-B8,DR3 of serum IgA levels could be related to the high incidence of autoimmune disorders among females and HLA-B8,DR3-positive individuals. The results showing higher levels of IgE in HLA-DR2-positive subjects might be consistent with the observation of a strong association between HLA-DR2 and IgE immune hyperresponsiveness to some allergen(s).