Circulating T lymphocytes from patients with rheumatoid arthritis (RA) were found to produce low concentrations of interferon-gamma (IFN-gamma) and express low amounts of this messenger RNA (mRNA) in response to stimulation with phytohemagglutinin (PHA). In this study, we have examined the superinduction effect of cycloheximide (CHX) on the IFN-gamma mRNA expression in PHA-stimulated T lymphocytes from nine patients with active RA compared to three healthy individuals. When CHX was added 6 hr postactivation, the expression of IFN-gamma mRNA in RA patients increased significantly at 24 and 48 hr (P less than 0.01) and reached levels similar to those observed in controls. We suggest that posttranscriptional events could play a role in the defective production of IFN-gamma observed in RA.