Sixteen patients with definite or classical Rheumatoid Arthritis (RA) of less than twelve months duration were recruited into a randomised, open twelve month study comparing Rifampicin 600 mg daily (9 patients) with Hydroxychloroquine (HCQ) 400 mg daily (7 patients). Ten patients completed twelve months of treatment (4 Rifampicin, 6 HCQ). Five patients were withdrawn from the study due to lack of efficacy (1 HCQ, 4 on Rifampicin). One further patient on rifampicin was withdrawn due to development of abnormal liver function tests. Significant improvement (p < 0.03) was noted in the Stoke Index (SI) at six and twelve months in the HCQ group which was not seen in the rifampicin group. In both groups there was no significant improvement in the single variables (Ritchie index, morning stiffness, grip strength, synovitis score, ESR, CRP). The results fail to confirm that Rifampicin may be useful in the treatment of RA in early stages of disease.