Chromosomal changes were assessed in 19 patients with rheumatoid arthritis (RA) treated with CPH82, a benzylidated podophyllotoxin glycoside, for up to one year. The frequency of chromosomal aberrations (CA) and sister chromatid exchanges (SCE) in peripheral lymphocytes increased significantly after 12 weeks of treatment and remained elevated after 48 weeks treatment in peripheral lymphocytes. The number of CA and SCE were significantly increased in CPH82 treated patients compared with the RA patients treated with other disease modifying anti-rheumatic drug (sulphasalazine, gold, D-penicillamine, azathioprine, methotrexate, cyclophosphamide). Only two patients treated with cyclophosphamide and azathioprine had changes of comparable levels. The results of this study suggest a mutagenic potential of CPH82 similar to that described for other immunosuppressive drugs and the newer podophyllotoxin derivatives, etoposide and teniposide.