There is an increasing evidence that T helper lymphocytes (CD4+) play a key role in the etiopathogenesis of type 1 diabetes. The aim of the present study was to evaluate the presence of T helper lymphocyte subpopulations: naive (CD4+CD45RA+), memory cells (CD4+CDRO+) and lymphocytes coexpressing both studied phenotypes (CD4+CD45RA+CD45RO+) in subjects at risk of type 1 diabetes (first degree relatives of IDDM patients with autoantibodies) in comparison to age and sex matched controls. We observed higher percentages of lymphocytes coexpressing CD45RA and CD45RO antigens in peripheral blood of first degree relatives with "pro-diabetogenic" DRB1*0401 allele and/or with impairment of first phase of insulin release (FPIR) in IVGTT. The CD4+CD45RA+/CD4+CD45RO+ cells ratio was significantly lower in subjects with protective DQB1*0602 alelle and/or higher FPIR levels. The alterations of CD45RA and CD45RO antigens expression on T helper cells in prediabetics suggest the significant role of naive or/and memory CD4+ T cell subsets in the pathogenesis of diabetes type 1. It could be suggested that CD4+CD45RA+/CD4+CD45RO+ ratio could serve as surrogate marker of diabetes type 1 risk development and presumably for estimation of the efficacy of the preventive procedures in subjects at high risk of IDDM, but further prospective studies are needed.