A new approach to prepared chemically modified chitosan sulfate derivatives was reported, from which chitosan sulfate was prepared from chitosan first. Then N-acyl or N,O-quaternary ammonium groups were introduced by the reaction of chitosan sulfate with caproic anhydride, propanoic anhydride, or 2,3-epoxypropyl trimethylammonium. The structures of the derivatives were characterized by elemental analysis, FT-IR, C-13 NMR, H-1 NMR and gel permeation chromatography. The antibacterial activities against Escherichia coli, which is a gram-negative bacterium, and Staphylococcus aureus, which is a gram-positive bacterium, have been investigated by optical density method. It was found that the chitosan sulfate showed no inhibition against E coli, while at concentration below 10(2) mug/ml its inhibition against S. aureus was higher than phenic acid, a widely used biocide. The quaternized derivatives of the chitosan sulfate also showed S. aureus inhibition but no E. coli inhibition. The acylated chitosan sulfates were found to be not only increasing the S. aureus inhibition activities but also exhibiting some inhibition towards the growth of E coli slightly. The activities of N-acyl chitosan sulfates seem to be related to the structures of the covalently bonded acyl moieties, among which the N-hexanoyl moiety was more effective in enhancing the E. coli inhibition activities. The antibacterial mechanism of the chitosan sulfate and its derivatives was also simply discussed. (C) 2003 Elsevier B.V. All rights reserved.