Cancer cachexia is a syndrome of progressive wasting which has been suggested to be mediated by cytokines such as tumor-necrosis factor-a, interleukin-1, interleukin-6 and interferon-g. Adittionaly, evidences have shown that proteoglycan-like molecules (azaftig and PIF) may act as direct mediators of the syndrome. Despite of the fact that macrophages constitute an important source of cytokines, there are no data available on the production of proteoglycans by immune cells in the cancer state. Also, the biological role of these macromolecules in inflammation is poorly understood. Therefore the aim of the present study was to investigate the following aspects of macrophages from tumor-bearing cachectic rats: morphological characteristics, phagocytic capacity and proteoglycans production. The Walker-256 carcinosarcoma was used as experimental model of cancer cachexia. Rats that were to become tumor-bearing received 2x10⁷ cells subcutaneously in the right flank fourteen days before macrophages harvesting by peritoneal lavage and experiments performing. Healthy rats were used as controls. Macrophages from tumor-bearing rats presented morphological characteristics of activated cells and also a higher phagocytic activity. After 24 hours of cell exposure to ³⁵[S]Sulfate almost 85% of total proteoglycan synthesized by normal and tumor-bearing rat macrophages were in the extracellular compartment. Both cell and medium fractions were collected and characterized by enzymatic degradation with specific mucopolissacharidases. The incorporation of ³⁵[S]Sulfate into proteoglycans was 40% increased when the cells were obtained from cachectic animals. Macrophages from tumor-bearing rats showed a 3.5-fold increase in medium heparan sulfate proteoglycans and a 2.4-fold increase in cell-associated dermatan and chondroitin sulfate proteoglycans. These results indicate that there is a positive relationship between macrophage activation and proteoglycan production in  peritoneal macrophages from Walker-256 tumor-bearing animals. The increased proteoglycan synthesis reported in this paper also suggests that azaftig and PIF, proteoglycan-like cachexia mediators, may be derived from immune cells like macrophages.