More aggressive therapy including cytotoxic drugs is increasingly used in the treatment of rheumatoid arthritis (RA), and may confer increased susceptibility to infections. Septic arthritis is one infectious complication known to be overrepresented in RA. We studied the impact of disease severity and medication in a group of nine RA patients with proven septic arthritis, excluding those occurring as a complication of orthopaedic surgery. Two control groups were used for comparison. The septic arthritis patients were functionally more incapacitated and more often treated with cytotoxic drugs. Six of the nine septic arthritis patients had received an intra-articular injection into the infected joint within 3 months prior to the onset of the septic arthritis. Only one of these occurred immediately after arthrocentesis. The annual frequency of septic arthritis was approximately 0.2%. During the 4-year period studied the frequency was 0.5%. When related to the number of glucocorticosteroid injections, a frequency of 1 per 2000 injections was found when late septic arthritis was included. The high frequency of delayed septic arthritis after intra-articular glucocorticosteroid administration should alert physicians to this complication.