Acetylator phenotype has been determined with sulphamethazine (sulphadimidine) in 69 Spanish patients with rheumatoid arthritis (48 females), all of whom were on second line therapy, and in 96 age-matched normal controls (54 females). Thirty-two patients (46.4%) and 56 controls (58.3%) were classified as slow acetylators. On analysing separately the females in both groups, 37.5% of patients and 63% of controls were found to be slow acetylators. No difference was found in the males (patients 66.3% and controls 52.4% slow acetylators). Rapid acetylator phenotype may be a risk factor for the development of severe rheumatoid arthritis in women.