In this study interleukin 2 (IL-2) synthesis by human lymphocytes in the presence and absence of prednisolone in a group of normal subjects has been assessed. An association between suppression in vitro of induced phytohaemagglutinin-blastogenesis by prednisolone and synthesis of IL-2 was found. Those subjects whose lymphocytes are identified as steroid-resistant have significantly higher IL-2 activity in the supernatants of both steroid and non-steroid treated lymphocyte cultures than steroid sensitive subjects. The addition of exogenous IL-2 was found to ablate the suppressive effects of steroids on lymphocyte blastogenesis. These results suggest that significantly greater activity of IL-2 in the culture supernatants of steroid resistant subjects may represent a mechanism for glucocorticoid resistance in vitro and help explain the relationship between increased loss of grafts and steroid resistance in renal allograft recipients.