We treated 5 patients diagnosed with rheumatoid arthritis (RA) with nitrogen mustard (HN2) and monitored clinical and immunologic variables. HN2, 0.3 mg/kg ideal body weight was given over 7 days. Disease activity and immune function were monitored during and after treatment. Duration of morning stiffness (p = 0.0044), joint count (p = 0.0140), and assessment of pain (p = 0.0264) and function (p = 0.0057) improved by Day 6. T lymphocytes (p = 0.0060), especially T memory cells (CD4CD29; p = 0.0017) fell dramatically. HN2 is effective for rapidly gaining control of active RA. This effect is T cell specific.