In the present study we have evaluated the association of HLA-DR antigens with circulating leukocyte levels in 113 HLA-typed normal healthy Sicilians. By two methods of statistical analysis (chi 2 test and Student t test) it has been possible to demonstrate clearly a significant association between high levels of mononuclear cells and HLA-DR1 phenotype. This increased number of mononuclear cells in HLA-DR1-positive subjects is due to the increase of blood T cells, whereas monocytes, B cells, neutrophils, and eosinophils are unmodified. These data are consistent with the hypothesis that HLA-DR-linked gene(s) are involved in the control of blood T-cell levels.