The lymphokine-activated killer (LAK) cell activity in the peripheral blood of 23 patients with rheumatoid arthritis has been studied. Two control groups comprised (a) nine patients with another chronic inflammatory disease (sarcoidosis) and (b) 19 normal healthy volunteers. The LAK activity induced by human recombinant IL-2 was very similar in controls and patients with rheumatoid arthritis but was significantly decreased in patients with sarcoidosis, although the frequency of LAK-cell precursors measured using a limiting dilution assay was comparable in all three groups. The DNA synthetic response of peripheral blood mononuclear (PBM) cells to IL-2 was slightly decreased in patients with both rheumatoid arthritis and sarcoidosis as compared to controls, but this decrease was not statistically significant. Spontaneous DNA synthesis in PBM cells cultured in the absence of IL-2 was essentially identical in all three groups. We conclude on the basis of these results that the higher risk of non-Hodgkin’s lymphomas in patients with rheumatoid arthritis cannot be attributed to an impairment of LAK activity. Furthermore, the doses of gamma-irradiation, which abolished the ‘background’ cytotoxicity of PBM cells cultured without IL-2 and also blocked effectively both spontaneous and exogenous IL-2-dependent DNA synthesis, had little effect on the generation of LAK activity. These observations are discussed in regard to the role of non-specific cytotoxic cells and the therapeutic efficacy of antiproliferative drugs in rheumatoid arthritis.