Polysaccharides isolated from the gel of Aloe species have been known to have diverse biological activities, including immunomodulatory and antitumor activities. The molecular size-immunomodulatory activity relationship of modified Aloe polysaccharide (MAP) was examined in this study. Crude MAP (G2E1) was prepared from the gel of Aloe vera that was partially digested with cellulase. Proteins in crude MAP were removed by passage through a DEAE-Sephacel column, and then the protein-free MAP (G2E1D) was further separated into three fractions, G2E1DS3 molecular weight (MW > or = 400 KDa), G2E1DS2 (5 KDa < or = MW < or = 400 KDa), G2E1DS1 (MW < or = 5 KDa), by Sephacryl column chromatography and ultrafiltration. Immunomodulatory activities of MAP preparations were examined on a mouse macrophage cell line, RAW 264.7 cells, and in ICR strain of mouse implanted with sarcoma 180 cells. We found that polysaccharides between 400 and 5 KDa exhibit the most potent macrophage-activating activity as determined by increased cytokine production, nitric oxide release, expression of surface molecules, and phagocytic activity. In accordance with the in vitro activity, polysaccharides between 400 and 5 KDa also exhibited the most potent antitumor activity in vivo.