Recurrent infections are common features in patients affected by various aminoacidopathies. Since these disorders are biochemically characterized by tissue accumulation of amino acids, it is possible that these compounds may act as immunosuppressants. We therefore investigated the influence of 21 amino acids on in vitro cellular growth of lymphocytes stimulated with phytohaemagglutinin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM), a recognized test of cellular immunocompetence. Human peripheral lymphocytes were cultured in flat-bottomed 96-well microplates at 37 degrees C for 96 (PHA and Con A) or 144 h (PWM) in the presence of one mitogen at different concentrations and of one amino acid added at doses of 2, 4 or 8 mM. Cell reactivity was measured by the incorporation of tritiated thymidine into cellular DNA and compared to that of identical cultures with no amino acids added (controls). We found that among the 21 amino acids tested, cysteine stimulated lymphocyte growth, whereas glutamate, tryptophan, phenylalanine and glutamine caused significant inhibition. These results may reflect an immunomodulatory role for some amino acids.