Intracellular thiols (LSH), superoxide dismutase (SOD) and plasma thiols (PSH) are thought to have an important role in the protection of tissues from damage by oxygen-derived free radicals. The change in the levels of activity of these substances in patients with active rheumatoid arthritis treated with sulphasalazine for 6 months was assessed in 22 patients. Over this time there was a marked improvement in disease activity. This was accompanied by an early increase in red cell LSH and decrease in SOD, although by 6 months these changes had completely reversed. In addition the negative correlation between these indices at week 0 had disappeared by week 6. Over the 6 months there was a steady rise in PSH. The change in PSH is slow and is thus more likely to reflect a change in the disease process rather than an active role for the thiol, but the early changes in intracellular parameters may be of importance in the action of this drug. These changes are similar to changes found with other second-line drugs. It is also of interest that a drug which does not itself possess a thiol group is capable of altering the thiol status of cells.