To investigate the mechanisms of cell mediated immunity to malaria, we studied different systems to measure specific activation of T lymphocytes by P. chabaudi antigens. Mice were primed by subcutaneous administration of parasite antigens followed by co-cultivation of lymphocytes taken from the draining lymph nodes in the presence of the priming antigen. A marked proliferative response was observed which was shown to be antigen specific, T-cell mediated and accessory cell dependent. Continuous T-cell lines were propagated in culture by repetitive restimulation in the presence of antigen and accessory cells, followed by expansion in a conditioned medium containing T-cell growth factors. These lines could be induced to proliferate to the priming antigen only in the presence of syngeneic accessory cells thus indicating that H-2 restriction operates in the recognition of plasmodium antigens by T cells. We also induced parasite specific T cells by the use of an in vitro primary 'education' system. Lymphocytes from unprimed mice were sensitized on parasite-fed macrophages and were then injected subcutaneously into each hind foot pad of syngeneic animals. This led to recruitment of antigen-reactive cells which were assayed in vitro by the ability of lymphocytes taken from the draining popliteal lymph nodes to proliferate in response to the sensitizing antigen. In vivo immunization with Plasmodium antigen fed macrophages also signalled antigen specific T cells that recruited reactive T cells in the draining lymph nodes.