Interleukin 1 beta (IL-1beta) is a proinflammatory cytokine that is considered to play an important role in the progression of rheumatoid arthritis (RA). A stimulus such as ATP is necessary to cause the release of mature IL-1beta, via activation of the P2X(7) receptor on monocytes. In this study, the production of IL-1beta in whole blood after ATP stimulation and expression of P2X(7) receptors in RA and healthy subjects were examined. Blood samples from RA patients or healthy controls were stimulated with ATP in the presence of lipopolysaccharide (LPS). Supernatants were harvested and IL-1beta levels were measured by enzyme-linked immunosorbent assay (ELISA). Expression of P2X(7) receptors was measured using flow cytometry. ATP induced significantly higher levels of IL-1beta in LPS-activated RA blood samples compared to controls. A significant up-regulation of P2X(7) receptor expression on mononuclear cells was observed after overnight incubation with ATP without any significant differences between RA patients and normals. These data suggest that RA patient mononuclear cells are more sensitive to ATP stimulation than healthy individuals perhaps due to genetic polymorphism in the P2X(7) gene.