Using site-directed mutagenesis method,six human interleukin-2 (IL-2) muteins with markedly reduced bioactivities were obtained,among them two muteins 15Val-IL-2 and 126Asp-IL-2 could decrease the biological effect of wild-type IL-2 in a specific concentration range. In assays of competition inhibition to high-affinity IL-2 receptor(IL-2R),15Val-IL-2 and 126Asp-IL-2 exhibited significant competitive abilities once again. These results showed that 15Val-IL-2 and 126Asp-IL-2 could partially antagonize the function of wild-type IL-2. Taking the analysis of IL-2 secondary structure and the knowledge of interaction between IL-2 and IL-2R into consideration，it may be concluded that the partial antagonism of 15Val-IL-2 and 126Asp-IL-2 lies in that substitution slightly disturb the tertiary binding microenviroment of IL-2 and IL-2R βγ subunits，thus interfering the binding of relevant IL-2 residues with IL-2R βγ subunits which yet is insufficient to totally disrupt such binding.