The activity of recombinant interleukin-2 (rIL-2) on the in vitro lymphocyte proliferative response to phytohemagglutinin mitogen was investigated in healthy HLA-B8,DR3 positive and negative subjects. The response to mitogen, significantly decreased in HLA-B8,DR3 positive subjects, was completely restored by adding rIL-2. Moreover, in HLA-B8,DR3 positive subjects the in vitro treatment with rIL-2 significantly increased the reduced frequency of mitogen responsive T lymphocyte precursors, as assessed by limiting dilution analysis. These data suggest that a decrease in the size of the pool of T cell precursors able to produce IL-2 is responsible for the impairment of T cell function observed in HLA-B8,DR3 positive subjects. Since in autoimmune diseases it is possible to show the same impairment(s) of T cell functions which can be observed in HLA-B8,DR3 positive subjects, these results could be of practical value for the understanding of pathogenetic mechanism(s) of autoimmune diseases and, in case, for therapeutical purposes.