This report addresses the role of individual IL-2 binding proteins of the IL-2 receptor in the stimulation of cell proliferation by IL-2. Murine IL-3-dependent cell lines were established which expressed the human p75 IL-2-binding protein, in the absence or presence of the human p55 IL-2-binding protein. Whereas p75 expression was sufficient to confer response to an intermediate (half-maximal stimulation at 100 pM) concentration of IL-2, additional expression of p55 increased the sensitivity of the cells to half-maximal stimulation at 10 pM IL-2. A mutant IL-2 molecule, Lys-20 IL-2 which is known to be defective of p75 interaction, was unable to stimulate cells expressing only p75: p55 co-expression could restore its activity. Under conditions of low p75 expression, Lys-20 IL-2 could act as an antagonist of wild-type IL-2 action. These data support a role for p55 in the enhancement of responsiveness to IL-2.