Abstract In vitro production of interleukin-2 (IL-2), IL-4, IL-5 and interferon-γ (IFN-γ) by splenocytes stimulated with concanavalin A (ConA) was studied in senescence-accelerated mice (SAMP8; 2–14.5 months old) by employing AKR (2–9 months old), origin of SAM strain, as controls. Male and female SAMP8 mice showed an age-related decrease in IL-2 production from the age of 9 months and the phenomena were accompanied by an increase in IFN-γ production with a large increment. AKR mice showed no decrease in IL-2 production even at 9 months of age, but there was an increase in IFN-γ production showing levels lower than those in SAMP8 mice. Between IL-2 and IFN-γ production during the ages of 2–9 months, there were negative correlations in male and female SAMP8 mice and a positive correlation in female AKR mice. The levels of IL-4 production were lower in SAMP8 than in AKR mice, although there was no difference in IL-5 production between SAMP8 and AKR mice. Male and female SAMP8 mice showed a positive correlation between IL-5 and IFN-γ production. Only in SAMP8 females was an increase in IFN-γ accompanied by an increase in IL-4. From these changes in teh cytokine production profile was it concluded that SAMP8 mice were senescence-accelerated in immuno-responses in comparison with AKR mice and had some functional deficiency with respect to IL-4 production, a part of which resulted from over-production of IFN-γ.