A family of water-soluble, negative-tone, high-resolution, chemically amplified photoresists based on partially or fully deprotected poly( 1,2:5,6-di-O-isopropylidene-3-O-methacryloly-alpha-D glucofuranose) is described. Both the molecular weight of the parent ketal-protected polymer and the extent of its deprotection to a water-soluble polymer containing 3-O-methacryloyl-D-glucopyranose repeat units must be carefully controlled to provide good coating and imaging properties. The two ketal protecting groups of the poly(1,2:5,6-di-O-isopropylidene-alpha-D-glucofurancose have different reactivity, and their complete removal requires long reaction times under hydrolytic conditions. The detailed deprotection chemistry of the polymer is readily understood through model studies with the fully and partially protected analogues of the polymer pendant groups: 1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose and 1,2-isopropylidene-alpha-D-glucopyranose. When combined with a water-soluble photochemical precursor of acid such as (4-methoxyphenyl)dimethylsulfonium trifluoromethanesulfonate, films of the deprotected or partially deprotected poly(1,2:5,6-di-O-isopropylidene-3-O-methacryloyl-alpha-D-glucofuranose) undergo acid-catalyzed cross-linking. The enhanced performance of the partially deprotected polymers over that of poly(3-O-methacryloyl-D-glucopyranose) suggests that the presence of remaining hydrophobic groups that afford water dispersibility rather than full solubility may be key to their performance. Imaged negative-tone features as small as 0.2 mu m are obtained with these materials that have sensitivities of ca. 30 mJ/cm(2) with wholly aqueous casting and processing.