Interleukin-2 (IL-2) production in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) was assessed at varying cell densities from 3 X 10(3)-1 X 10(5) cells/culture in response to mitogen stimulation, using a cellular interleukin assay in which IL-2 responsive CTLL-2 indicator cells were added directly to stimulated peripheral blood lymphocyte cultures. It was found that in both RA and SLE there was a significant overproduction of IL-2 demonstrable at low cell densities. At high cell densities, IL-2 production was decreased in SLE but remained enhanced in RA. The former abnormality appears to be related to disease activity and was not reversed by irradiation, suggesting that it is not the result of the actions of a radiation sensitive suppressor cell population. The possibility is discussed that a local hyper-production of IL-2 could induce disturbances of the immune response, resulting in the breaking of normal tolerance.