This report describes the isolation, and the phenotypic and functional characterization of Plasmodium falciparum-specific human T lymphocyte clones (TLC) obtained from 2 acutely infected and 4 clinically immune donors. Approximately one third of the TLC obtained from the acutely infected patients had the phenotype CD8+/CD4-. No such clones were obtained from the clinically immune donors. P. falciparum-specific, major histocompatibility complex-restricted CD8+ clones can lyse unrelated tumor cell targets in the presence of anti-CD3 antibodies, suggesting that these clones have cytotoxic potential. Conversely no killing was obtained with two CD4+ P. falciparum-specific TLC, even in the presence of anti-CD3 antibody, In addition the helper function of a CD4+ clone was demonstrated in a T/B cell cooperation system.