A series of cross-linkers [N,N'-methylenebisacrylamide (Bis), N,N'-(1,2-dihydroxyethylene)bisacrylamide (DHEBA), N,N'-diallyltartardiamide (DATD) and N,N'-bisacrylylcystamine (BAC)] were investigated as potential candidates of a novel class of polyacrylamide amide matrices, exhibiting high hydrophilicity, high resistance to hydrolysis and larger pore sizes than conventional polyacrylamide gels. The most hydrophilic cross-linker (DATD) exhibited first-order degradation kinetics in 0.1 M NaOH, suggesting that such a structure is electronically unstable, whereas the other cross-linkers displayed first-order kinetics. In addition, when used in highly cross-linked gels (for increasing pore size), DATD acts as an inhibitor of gel polymerization. Another interesting finding is an inverse relationship between the partition coefficient of such cross-linkers and the incorporation efficiency; the more hydrophobic members of the family exhibit a reduced conversion from monomer into polymer, which is more pronounced in highly cross-linked gels. When measuring the partition coefficient, DATD and DHEBA appear to be highly hydrophilic whereas BAC, owing to the two sulphur atoms in the molecule, appears to be extremely hydrophobic. The use of BAC in gels for protein separations should therefore be avoided.