Sera from 16 of 20 patients with AML at some stage of the disease inhibited the in vitro PHA transformation of normal lymphocytes assessed by measuring the rate of DNA synthesis after 67-70 hours; 42% of pretreatment sera were inhibitory. Inhibitory activity was overcome at PHA concentrations 2-3 times greater than the concentration which allowed maximum discrimination between NHS and leukaemia sera.PHA transformation of washed lymphocytes obtained from AML patients before treatment and when receiving induction or consolidation (cytoreductive) chemotherapy was reduced only when cultures contained a high proportion of primitive cells. Even in primitive cell contaminated cultures significant responses to PHA could be measured if conditions were modified to prevent increasing acidity.Reports of reduced in vitro immunological reactions in pretreatment and poor prognosis patients may therefore be due to the presence of primitive cells in culture, and in treated patients to the failure of chemotherapy to reduce the circulating primitive cell count. Serum inhibitory factors may have a significant immunosuppressive effect in vivo, but the accurate assessment of the role of immune mechanisms in AML should attempt the measurement of specific immunity.