Interleukin-2 (IL-2) has been proven to be a defective element in immune regulation in systemic lupus erythematosus (SLE). However, its course in time is unknown. We studied its production and cellular response in the peripheral blood cells of 30 SLE patients and 12 healthy subjects. In addition, we studied the spontaneous and lipopolysaccharide (LPS) induced production of IL-1, which have been found to be, respectively, increased and lowered in untreated SLE patients. Patients were studied at the outset, when still untreated, and at 1, 2, 6, 12, 18, and 24 months. At the outset, 18 had active disease and 12 were in remission. The decreased proliferative response of T cells to IL-2 and the deficient production of IL-1 upon LPS induction became normal after 6 months treatment, whereas the expression of high affinity IL-2 receptors took 18 months to become normal and the deficient production of IL-2 took 2 years. Despite clinical remission, the decreased capacity of T cells to absorb IL-2 persisted for 2 years. The effect of various prednisone dosages on the measured variables was evaluated. With intermediate doses of prednisone (20-45 mg), we observed the largest improvement in IL-2 production and in IL-1 production upon LPS stimulation. Higher doses of prednisone reduced also the spontaneous production of IL-1 and resulted in an increase in the expression of CD25+ cells. The addition of low doses of cytotoxic drugs (oral cyclophosphamide or azathioprine) resulted in an improvement in the capacity to absorb IL-2 and a reduction in spontaneous IL-1 production.(ABSTRACT TRUNCATED AT 250 WORDS)