Azathioprine (AZA), a purine analog, is an effective agent in the treatment of rheumatoid arthritis (RA), but variability of response and sometimes life-threatening side effects limit its use (1). The metabolism of AZA parallels the endogenous purine pathways. In this paper we review some general aspects of purine and thiopurine metabolism, their relation with various disease states and current knowledge of the influence of purine enzymes on the effects of AZA treatment. We suggest that intracellular purine enzyme activities determine the response to AZA treatment in patients with RA, and that a role for purine enzyme activities in the ethiopathogenesis of RA should be considered.