An increase in circulating eosinophils was observed in patients with AIDS or ARC who were substituted for a period of 14 days with exogenous recombinant IL-2 in the context of a Phase I/II study. IL-2 exerts a broad range of biological properties and enhances the production of a variety of other cytokines, i.e., factors for haemopoietic cell growth and differentiation. After having excluded a direct effect of r IL-2 on haemopoietic precursor cells in semi-solid agar cultures, we developed a liquid culture system and studied the effect of patients' sera collected at different time intervals before, during and after r IL-2 substitution on cell differentiation of normal human bone-marrow cells in vitro. Patients' eosinophilia was preceded by a detectable activity in the sera which induced light-density, non-adherent bone-marrow cells to differentiate into the eosinophil lineage and was assessed by the presence of eosinophil primary granules or Luxol-fast blue positive granules. Thus, these in vitro data suggest the presence of circulating mediator(s) enhancing eosinophil production and differentiation in response to in vivo substitution of r IL-2.