Objective: Cloves (Syzygium aromaticum), the dried flower buds of a tree belonging to the Myrtaceae family have achieved a top place in herbal medicine. To its main active compound eugenol have been attributed definite anti-anaphylactic, anti-inflammatory, and even anticancer properties. It was the object of the study to elucidate the immunomodulatory potential of eugenol and its ability to alter the crosstalk between human peripheral blood mononuclear cells (PBMC) and cells from two human colon carcinoma lines. Materials and Methods: Eugenol, at concentrations of 3.75, 7.5, and 15 µg/ml, was added for 24 h to PBMC alone or to cells co-incubated with either HT-29 or RKO colon carcinoma cells. Subsequently, the generation of the following cytokines was examined: Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IFN-γ, IL-1ra, and IL-10. Results: Eugenol did not affect the capacity of unstimulated PBMC or that of cancer cells to produce any of the cytokines examined. However, when eugenol was added to PBMC co-incubated with HT-29 cells, the production of all cytokines was inhibited, except for IL-6 and IFNγ. The capacity for cytokine generation by PBMC co-incubated with RKO cells was reduced concerning TNF-α and IL-1β. Conclusions: The results indicate that eugenol exerts an immunomodulatory effect on PBMC to produce inflammatory cytokines when stimulated by colon carcinoma cells from the two lines examined. This effect has been shown to be cancer cell type dependent. The capacity of eugenol to interfere with the crosstalk between immune and colon cancer cells may further explain the restraining effect of this compound on cancer development.