Efficacy and safety of azathioprine in 'high' and 'low' dose regimens in rheumatoid arthritis (RA), both in short-term studies and in follow-up over 40 months, have previously been shown. In the present report, 36 patients with RA treated with azathioprine (group I) and 49 age-matched patients with RA (group II), were studied to detect potential early markers of malignancy. Chest x-rays were similar to both groups. One patient in group I had a positive PAP smear and was subsequently found to have uterine carcinoma. Alpha-fetoprotein was positive in one patient in group I and none in group II. CEA was negative in all patients in group I, but positive in seven in group II. On chromosomal analysis group I showed a greater frequency of breakage. Group I showed lower serum folates and a highly significant number of megaloblastic features in marrow aspirates. In group I seven tumours, three being malignant, occurred while taking azathioprine, and in group II six tumours, one malignant, were identified (p = 0.17). The apparent increased risk of malignancy previously suggested by others warrants further studies with larger populations and over a continuous longer period.