Novel hydrogels based on N,N-dimethylacrylamide, N-t-butylacrylamide, and acrylic acid cross-linked with azoaromatic compounds of varying length and electron density of the azo bond were synthesized. The cross-links are degradable by microbial azoreductases present predominantly in the colon, and the gels appear to be suitable for colon-specific drug delivery. The degradability in vitro and in vivo was found to be related to the degree of swelling of the gels. The higher the degree of swelling, the higher the degradability. However, structural and electronic factors were also shown to influence reduction of azo bonds.