Abstract: C57BL/6J, NIH and ICR mice were inoculated with nonlethal P. yoelii (BY 265 strain) and NIH mice which had recovered from primary infection were reinocizlated with the same parasite. The parasitemia of the mice was observed and IL-2 production by spleen lymphocytes of the mice upon Con A or P. yoelii antigen stimulation was detected at different intervals throughout primary infection and reinfection. The IL-2 level was measured by the microassay bzsed on incorporation of H-TdR into CTLL2. The main results were as follows: (1) There were marked differences in both the Con A-induced IL-2 production and the parasitemia between C57BL/6J, NIH and ICR mice. The Con A-induced IL-2 levels (X± SE of SI) in C57BL/6J, NIH and ICR mice before primary infection were 223.7±19.32, 122.12±28.91 and 7226±30.60 respectively. The maximum parasitemia (X± SE of %) in C57BL/6J, NIH and ICR mice after primary infection were 2.7%±0.29%, 14.50% ±2.75% and 31.30%±1.80% separately. It suggests that the innate Con A-induced IL-2 levels in the three strains of mice might be one of the factors influencing their susceptibility to P. yoelii primary infection. (2) There was significant depression in the capacity of releasing IL-2 upon Con A stimulation 3, 10 and 15 days after NIH mice had been inoculated with P. yoelii; after that, it was followed by the gradual resumption of the Con A-induced IL-2 production. P. yoelii antigen-induced IL-2 was only detected by d34 after inoculation. In contrast, when NIH mice which had been recovered from primary infection were reinoculated with the same parasite, the animals were partly re3istant to reinfection and there was no decrease in Con A-induced IL-2 production after reinocu-lation and the enhancement of IL-2 production upon specific antigen stimulation 3 and 19 days after reinoculation. The findings suggest that the parasitespecific splenic lymphocytes capable of releasing IL-2 upon antigen stimulation appear in the late st?.ge of primary infection and the lymphocytes possessing memory function may elevate their capacity of secreting IL-2 during the course of reinfection. This phenomenon is considered to be related to regulation of protective immunity against malaria.