While tumor incidence increases with age, tumor growth and metastasis often proceed at a slower rate in aged organisms. The mechanisms underlying this age-related reduced tumor development may suggest therapeutic modalities appropriate for the aged. Decreased tumor aggressiveness in the old was shown to be related to altered immune response. Consequently, the aim of the present study was to assess whether cancer immunotherapy has an age-dependent effect. Only a few studies have compared cancer immunotherapy efficiency as a function of age, most showing lower inhibition in older animals. In the present study, we tested the effect of two immunomodulators, levamisole and BCG, on two tumors, B16 melanoma and AKR lymphoma, in mice of different ages. We demonstrated a higher efficiency of immunotherapy in aged as compared to young mice, particularly at low immunomodulator doses. While decreased T cell function during aging is apparently established, nonspecific immunity is more preserved or even enhanced in later life. We found an increased number of macrophages in tumors of old compared to young mice and an increase in MAC-1+ cells in old levamisole-treated compared to non-treated mice. The stronger therapeutic effect of this immunomodulator in old mice might thus be due to an increased macrophage-mediated anti-tumoral effect.