Forty-eight cases of systemic lupus erythematosus (SLE) were studied for lymphocyte subpopulations, and 42 cases were studied for lymphocyte response to mitogen stimulation. A decreased percentage of thymus-derived cells (T cells) and an increased percentage of bursa-equivalent derived cells (B cells), null cells (N cells), double labelled cells (D cells) were found in non-treated cases of SLE. There was no significant difference in these lymphocyte subpopulations in the treated cases in comparison with the normal control. There was an inverted linear relationship between T cells and N cells (p less than 0.001). No such relationship was found between B cells and N cells. The lymphocyte transformation in response to phytohemagglutinin (PHA), pokeweed mitogen (PWM) and concanavalin A (Con A) was expressed in three ways: (1) the net count of transformed data, (2) the difference between the square roots of the isotope incorporation in the stimulated and the non-stimulated cultures (Dsq), and (3) the stimulation index (SI). There were significantly decreased lymphocyte transformation in response to PHA, PWM stimulation in both the non-treated and the treated cases of SLE when results were expressed as net count and Dsq. But decreased counts in response to Con A was only found in non-treated cases. In contrast, no significantly lowered response to all three mitogens was found when data were expressed as stimulation index. Simultaneous study of the percentages of T cells, B cells, N cells, and D cells might be helpful in assessing the clinical activity of SLE and monitoring the effect of therapy. In the study of lymphocyte response to mitogen stimulation, Con A response was a more sensitive indicator of disease activity. The stimulation index was not a good method to demonstrate the result of lymphocyte response to mitogen stimulation in cases of SLE.