We have investigated the effect of orally administered Lactobacillus casei Shirota (L. casei) on immunological memory, as measured by delayed-type hypersensitivity (DTH) and acquired cellular resistance (ACR). The studies were performed in animal models in which the animals were rendered immune by a primary Listeria monocytogenes infection. It was shown that orally administered viable L. casei, and not heat-killed L. casei, enhanced significantly the antigen-specific DTH at 24 and 48 h in Wistar rats, Brown Norway rats, and BALB/c mice in a time-and dose-dependent fashion. L. casei had to be administered at least 3 days prior to the DTH assay at a daily dose of 10 9 CFU in order to induce significant effects. Long-term administration of 10 9 CFU of viable L. casei resulted in enhanced ACR, as demonstrated by reduced L. monocytogenes counts in the spleen and liver and diminished serum alanine aminotransferase activity after reinfection. Enhancement of cellmediated immunological immune responses by L. casei was further established in an adoptive transfer study. Naïve recipient BALB/c mice, which were infused with nonadherent, immunized spleen cells from L. casei-fed donor BALB/c mice, showed significantly enhanced DTH responses at 24 and 48 h compared to recipient mice which received spleen cells from control donor mice. In conclusion, orally administered L. casei enhanced cell-mediated immunological memory responses. The effects relied on lactobacillus dose and viability as well as timing of supplementation and, further, appeared to be independent of host species or genetic background.Various cells of the innate and acquired immune system interact in a concerted fashion to constitute a sophisticated set of responses to protect the physiological integrity of the host against infectious agents and tumors. Inappropriate orchestrated immune responses lead to, e.g., autoimmune and allergic disease states as well as enhanced susceptibility to infections. Different compounds are known which have the capacity to enhance or decrease biological responses of the immune system in order to restore disturbed immune responses or to elevate resistance to infectious agents. These compounds can be classified as so-called immunomodulators or biologic response modifiers (23).Lactobacilli form a source of potential modulators of the immune system. It has been demonstrated that specific Lactobacillus strains can modulate host immunity, which positively correlates with enhanced resistance to various viral and bacterial infections (9,20,24). The immunomodulating effects are dependent on various factors, such as intrinsic adjuvanticity properties (21), dose (13, 31), viability (16, 20, 30), route and timing of administration of the specific Lactobacillus strains (i.e., oral versus parenteral), and the physiological state and genetic background of the host (20).Previous results from our group established that 10 9 orally administered viable Lactobacillus casei Shirota strain YIT9029 (L. casei) bacteria given daily enhanced Trichinella spi...