A series of sage phenolics was tested for activity against a panel of Leishmania parasites and for immunomodulatory effects on macrophage functions including release of tumour necrosis factor (TNF), interleukin-6 (IL-6), and interferon (IFN)-like activities. For this, functional bioassays were employed including an in vitro model for leishmaniasis in which macrophage- like RAW 264.7 cells were infected with Leishmania parasites, an extracellular Leishmania growth-inhibition assay, a fibroblast-lysis assay for TNF-activity, a cell proliferation assay using IL-6 sensitive murine B9 hybridoma cells, and a virus protection assay for IFN-like activity. Whereas none of the test samples exhibited marked activities against extracellular Leishmania promastigotes (IC50 > 700 to > 2800 nм; > 500 μg/ml), caffeic acid, salvianolic acids K and L as well as the methyl ester of salvianolic acid I showed pronounced antileishmanial activities against intracellular amastigote stages within RAW cells (IC50 3-23 nм vs. 10-11 nм for the reference Pentostam®). Noteworthy, the phenolic samples showed no cytotoxicity against the host cells (IC50 > 600 to > 2200 nм; > 400 μg/ml). Tested sage phenolics activated Leishmania-infected RAW 264.7 for release of TNF ranging 22-117 U/ml and IL-6 ranging 3-42 U/ml. In contrast, their TNF- or IL-6-inducing potential in experiments with non-infected host cells was negligible. Furthermore, caffeic acid and salvianolic acid K induced a modest release of IFN-like activity (5-9 and 2-4 U/ml, respectively) as reflected by inhibition of the cytopathic effect of encephalomyocarditis virus on L929 cells. The results support the emerging picture that plant polyphenols may be credited for the profound healthbeneficial properties of various herbal medicines and agricultural products.