To study the effect of hydroxychloroquine on cytokine production by monocytes and T cells, cells were pretreated with varying concentrations of hydroxychloroquine and stimulated with lipopolysaccharide (monocytes), phytohemagglutinin or anti-CD-3 monoclonal antibodies (T cells). Interleukin 1 alpha (IL-1-alpha), IL-6 and tumor necrosis factor alpha (TNF-alpha) production were measured from the stimulated monocytes and IL-2, IL-4 and gamma interferon (IFN-gamma) were measured from the stimulated T cells. Hydroxychloroquine inhibited production of IL-1-alpha (monocytes) and IL-6 (T cells and monocytes). In contrast IL-2, IL-4, TNF-alpha and IFN-gamma production were not affected. Preferential inhibition of IL-1-alpha production by monocytes and IL-6 production by T cells and monocytes may contribute to its antiinflammatory effect in autoimmune diseases.