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The mitogen-induced DNA synthesis in vitro in lymphocytes from 20 patients acutely ill with Plasmodium falciparum malaria was compared with that of 16 healthy donors. Within both groups part of the donors were individuals who had only experienced short exposure or none at all to the parasite (Sweden) while the other part were donors living in a malaria endemic area (Colombia), The proliferative response to the T cell mitogen La (leucoagglutinin from PHA) of the patients was significantly reduced as compared with that of the controls. With pokeweed mitogen which stimulates T cells and induces a T cell-dependent activation of B cells, no difference between patients or controls was seen. The results were similar for the donors of different geographical origin and malaria background. Lymphocytes and monocytes from the peripheral blood of these donors were also studied for surface marker distribution by means of monoclonal antibodies. Both the absolute and the relative frequencies of T cells in the blood of the malaria patients were significantly reduced as compared with the controls. Furthermore, in almost all eight patients tested, the ratio between T4+ T cells (including the helper/inducer subsets) and T8+ T cells (including the suppressor and cytotoxic subsets) were below 1: 1 while they were close to 2:1 in the controls. The results indicate that the relative frequency of T8+ T cells, expressed as percentage total T cells (T.3+ ) was significantly elevated in the P. falciparum patients. The possible relationship between this imbalance and the irregular La response of the patients lymphocytes requires further investigation of lymphocyte function. [ABSTRACT FROM AUTHOR]