In order to determine whether budesonide, which is believed to exert most of its anti-inflammatory effects in the intestinal tract, has a beneficial effect on disease activity in rheumatoid arthritis (RA), we treated 26 patients with active RA in double-blind fashion with either controlled ileal-release budesonide (9 mg by mouth) ( n=14) or placebo ( n=12). All patients remained on their existing disease-modifying antirheumatic drugs (DMARDs) and nonsteroidal anti-inflammatory drugs (NSAIDs). Paracetamol was used for escape analgesia. Evaluations were performed at 0, 2, and 4 weeks and included tender and swollen joint counts, duration of morning stiffness, visual analogue scale for pain (VAS) on a 100-mm horizontal scale, grip strength using a vigorimeter (lb/in(2)), haemoglobin, erythrocyte sedimentation rate (ESR) (Westergren method, mm/1st h), plasma viscosity (PV) in cP (normal range 1.5-1.72), C-reactive protein (CRP) (normal upper level 1 mg/dl), random plasma cortisol (nmol/l) drawn between 10 a.m. and 2 p.m., and blood pressure. Disease activity scores based on 28 joints (DAS 28) were also derived at all time points. Within-group comparisons revealed significant improvement in the budesonide-treated but not the placebo group with respect to numbers of tender and swollen joints, duration of morning stiffness, grip strength, pain, ESR, PV, and DAS 28. Between-group comparisons showed significant differences for ESR, PV, pain, and random plasma cortisol (drawn between 10 a.m. and 2 p.m.). There were no significant side effects in either group.