Previously, we found that chronic ingestion of the extract of coffee cherry (CC), the residue after the removal of coffee beans, induced a marked suppression of the development and the growth of spontaneous mammary tumours in a high mammary tumour strain of SHN mice. As a possible step to clarify the mechanism of this effect, the immunomodulating role of CC was examined in this study. CC treatment resulted in significant weight gain in the spleen. CC treated experimental mice showed a significant decrease in the proportion of immature (CD4+8+) thymocytes and an increase in the percentages of mature cells expressing helper/inducer (CD4+8-) or cytotoxic/suppressor (CD4-8+) phenotypes. The proportion of T cells expressing CD25, a lymphocyte activation marker, in the spleen and peripheral blood tended to increase in the CC treated group. The natural killer activity of the spleen cells was not affected by CC ingestion. These results have revealed that CC can enhance the differentiation of thymocytes and the activation of peripheral T lymphocytes.