Abstract Soluble fragments of starch microspheres, Spherex, having a molecular weight ranging from < 4 × 10 4 to 1 × 10 6 were obtained by degradation with α-amylase. The effects of the starch fragments on mouse peritoneal macrophages were compared with those of small starch microspheres (mean diameter 1.4 μm). Toxicity, rate of phagocytosis, protein and RNA synthesis, release of arachidonic acid, LTC 4 and PGE 2 were studied after exposure to different doses of the soluble fragments or the microspheres. No negative effect was seen on the number of adherent cells. Microspheres were rapidly phagocytosed whereas the soluble fragments were taken up at a considerably slower rate indicating fluid phase pinocytosis. Protein and RNA synthesis was significantly increased. Arachidonic acid metabolites were released from cells exposed to microspheres whereas the soluble fragments had no effect on the release of these inflammatory mediators. Neither the starch microspheres nor the fragments stimulated the macrophages to express cytostatic or cytocidal activity against the L-929 cells. The results indicate that fragments of epichlorhydrin cross-linked spheres, Spherex, are weakly stimulatory but non-toxic to macrophages.