The immunomodulatory actions of a water-soluble derivative of propolis (WSDP) and two components of propolis, caffeic acid (CA) and caffeic acid phenethyl ester (CAPE) were investigated. Oral administration (50 mg/kg) of WSDP, CA, and CAPE enhanced the weight and cellularity of the spleen (p<0.05, p<0.01) of treated mice. The response of spleen cells to polyclonal mitogens (PHA, Con A, PWM) was also increased in mice treated with WSDP as compared to control (p<0.01); in contrast, the response of spleen cells of mice treated with CA were significantly suppressed (p<0.001). The colony forming ability of HeLa cells plated on monolayers of macrophages was completely inhibited by peritoneal macrophages from mice receiving either WSDP, CAPE, or CA. Macrophages from treated mice also inhibited [3H]TdR incorporation into HeLa cells in vitro. Testing for the possible presence of NO in the supernatants of 24 hours cultured macrophages activated with either compound revealed that the toxicity of these cells to HeLa cells was in part due to the production of NO. Tumour growth was suppressed by WSDP and its polyphenolic compounds given orally to mice. Local presence of CA, and CAPE in the tissue, caused a significant delay of tumour formation. Based on these results, we postulate that the antitumour activity of the test compounds includes pronounced immunomodulatory activity mainly due to the augmentation of non-specific antitumour resistance in mice via macrophage activation and the production of soluble factors by those cells which may interfere with either cells of the immune system or directly by tumour cells.