The high-temperature reaction of macromolecules with tetra-alkylammonium hydroxides has significantly improved the use of the conventional pyrolytic procedures which are widely used for the structural characterization of natural biopolymers and geomacromolecules. This new pyrolytic approach has overcome some of the analytical limitations of conventional pyrolysis allowing the detection of polar compounds as their alkyl derivatives. We report recent developments of the high-temperature hydrolysis and alkylation procedure, carried out in the presence of tetra-alkylammonium hydroxides, for the structural characterization of natural biopolymers and geomacromolecules such as lignins, humic substances, coals, asphaltenes and kerogens.