An ELISA assay, designed to detect interferon-gamma (IFN-gamma) in the picogram range, was used to study the presence of IFN-gamma in serum and its production by T cells taken from C57BL/6 mice infected with Plasmodium chabaudi chabaudi. IFN-gamma was detectable in mouse plasma for two to three days before the peak of parasitaemia. Similarly, IFN-gamma production by T cells could be detected in vitro. In limiting dilution cultures, the production of IFN-gamma by as few as 1,000 T cells was detectable using this assay. The limiting dilution analysis revealed that a substantial IFN-gamma response by specific T cells occurs very early in a primary infection with P. chabaudi.