In the present study we have examined the potential contribution of IL-2/IL-2R interactions in CD3-mediated responses by T lymphocytes from patients with systemic lupus erythematosus (SLE). T-cells from SLE patients showed normal IL-2 production when activated with OKT3 MAb and submitogenic concentrations of PMA, in cultures in which uptake of endogenous IL-2 was prevented by pretreatment with anti-Tac MAb. In contrast, PHA-induced IL-2 production was lower in patients under the same conditions. Under these stimulatory conditions the proportions of T-cells expressing IL-2R CD25 molecules was comparable in patients and controls. There was earlier and higher binding of exogenously added IL-2 in T lymphocytes from patients activated via the CD3 pathway. Furthermore, these cells responded to IL-2 with stronger proliferative responses than cells from control subjects. These findings may partly explain the increased proliferative responses of SLE T-cells when stimulated via the CD3 pathway. © 1994 Academic Press. All rights reserved.