In the present study we examined the immune-enhancing effect of a nucleoside-nucleotide mixture on the non-specific T-cell immune functions of senescence-accelerated mice (SAM) fed on a low-protein diet. The immune functions studied were in vitro thymic and splenic cell lymphoproliferative responses to phytohaemagglutinin, lipopolysaccharide and concanavalin A and their production of interleukin-2 (IL-2) and interferon-gamma (INF-gamma) in response to mitogen stimulation. SAMP8 mice aged 3 and 6 months were used. In each age group, mice were fed on diets containing either 50 g casein/kg, 50 g casein/kg supplemented with 5 g nucleoside-nucleotide mixture/kg or 200 g casein/kg for 3 weeks. The supplemented 3- and 6-month-old mice had higher (P < 0.05) thymic and splenic cell counts compared with the low-protein group. In both age groups of mice, concanavalin A induced higher (P < 0.05) total thymic and splenic lymphoproliferative responses for the nucleoside-nucleotide mixture-supplemented group compared with the 50 g casein/kg dietary groups. Thymic and splenic production of IL-2 was higher for the 3-month-old mice in both the supplemented and the 200 g casein/kg dietary groups. INF-gamma production in the supplemented 3-month-old group and the 6-month-old 200 g casein/kg dietary group was higher (P < 0.05) compared with the other groups. Overall the supplemented 3-month-old mice exhibited both higher lymphoproliferative responses and production of cytokines compared with the supplemented 6-month-old mice. The results indicate that early nucleoside-nucleotide mixture supplementation may enhance the immune response in protein-deprived SAMP8 mice.