The cytotoxicity of dextran T40, methacrylated dextran (dex-MA) and hydroxyethyl-methacrylated dextran (dex-HEMA), dextran-based hydrogel discs and microspheres, and their degradation products, was studied by measuring the cell proliferation inhibition index (CPII) on human fibroblasts in vitro. In addition, during the 72 h incubation period light-microscopic observations were performed daily. After 24 h of incubation with dextran and dex-HEMA polymers, the cells showed elongated or spider-like forms, some lipid droplets and intracellular granula, indicative of pinocytosis and internalization of the polymers. During the next two days, the fibroblasts' appearance did not change. Methacrylic acid (MAA), formed by hydrolysis of dex-HEMA, did not influence the cell morphology. Dex-HEMA polymer solutions with a low and high degree of substitution (DS) at 100 mg/ml caused a CPII of 30-40% after 72 h. This is less than 10% growth inhibition per cell cycle and statistically not different from the CPII induced by 100 mg/ml dextran T40. Growth inhibition induced by MAA was also low. The various dex-MA hydrogel discs caused similar low growth inhibition. Interestingly, hydrogel microspheres of dex-MA and dex-(lactate-)HEMA caused a CPII of only 0-20% after 72 h. The results presented in this study demonstrate that methacrylate-derivatized dextran hydrogels show good biocompatibility in vitro making these degradable biomaterials promising systems for drug delivery purposes.