We have previously reported that nonsteroidal anti-inflammatory agents (NSAIAs) stimulate cellular immune responses and inhibit production of IgM rheumatoid factor in cultures of lymphocytes from patients with rheumatoid arthritis. We had 20 patients with rheumatoid arthritis stop taking NSAIAs for two weeks and then take piroxicam, a new NSAIA, for an additional ten weeks to assess the in vivo effects of NSAIAs on cellular immunity and rheumatoid factor levels. In each case, serum rheumatoid factor levels rose and phytohemagglutinin response fell when placebo was substituted for NSAIAs. Piroxicam administration was associated with a fall in rheumatoid factor levels to approximately 62% of the baseline level and with an increase in phytohemagglutinin response. The action of NSAIAs in rheumatoid arthritis may be mediated to a degree by partial correction of the disordered immunoregulation in this disease. © 1983, American Medical Association. All rights reserved.