Soluble CD23 (sCD23), a recently discovered multifunctional cytokine, is a 25-kDa molecule released by autoproteolysis from the 45-kDa CD23 molecule which is found mainly on the surface of B lymphocytes. In the present study we aimed to evaluate, in association with humoral immune and metabolic markers, the changes in CD23 antigen expression on B lymphocytes and levels of sCD23 in the peripheral blood of subjects at high risk of type 1 diabetes. The study was carried out in 28 first-degree relatives of type 1 diabetes patients (versus a control group of 28 age- and sex-matched healthy volunteers) using antibodies against different B-cell antigens: ICA, GADA, IAA, IA-2. Flow cytometry was used to measure the percentage of CD20+ (B lymphocytes) and CD20+CD23+ lymphocyte subsets, and sCD23 levels in serum were determined by enzyme immunoassay. Prediabetic subjects had a significantly (P<0.01) lower percentage of CD20+CD23+ lymphocytes in comparison with healthy age- and sex-matched controls. Expression of CD23+ on B lymphocytes was similar in subjects with ICA only and with two or more antibodies against pancreatic antigens. In the prediabetic group, the median concentration of sCD23 was lower than in the control group and was statistically significant (P < 0.02) in the subgroup of subjects with the most impaired function of pancreatic beta-cells (the lowest values of first phase of insulin release). In conclusion, our study suggests that CD23 molecule expression on B lymphocytes and sCD23 levels in peripheral blood could be additional markers for monitoring the development of type 1 diabetes and play a role in determining the efficacy of prevention trials. However, further prospective studies are needed.