A procedure has been described for the preparation of T and non-T lymphocyte populations. The purine nucleotide contents were analyzed by high-performance liquid chromatography. In healthy subjects the pattern was shown to be different in the two cell populations. In patients with rheumatoid arthritis the findings as compared with the healthy subjects were as follows; in T cells the RA patients showed a slight decrease in di- and tri-phosphates, a more significant decrease of NAD and an increase of AMP. The changes in non-T cells of the RA patients were highly significant and can be summarized as a generalized reduction of all nucleotides, except IMP which tends to increase, and GMP which remains constant. The variations observed in nucleotide content do not involve alterations of some parameters, such as the adenylates/guanylates, the ATP/ADP and GTP/GDP ratios and the energy charges for adenylates and guanylates, regarded as an index of cell energy and viability. It is possible that disturbances of purine metabolism, revealed through the determination of purine contents of lymphocytes, precede immunological events and could be useful in the study of immunologic disorders such as rheumatoid arthritis.