The catalytic mechanism of the HIV-1 protease (HIV-PR) is studied through ab initio theoretical model calculations. This model consists of a formate/formic acid pair, a structurally important water molecule, and a formamide molecule. The proposed catalytic mechanism is composed of five steps, two of which are transition states separated by a third step (an intermediate state). The remaining two steps are related to product release. The overall forward hydrolysis reaction barrier is approximately 22 kcal/mol, with a reverse hydrolysis barrier of approximately 34 kcal/mol at the RHF/6-31G* level. The second transition state is related to a nucleophilic attack of the water molecule on the carbon atom of the substrate scissile bond, and is essential for the collapse of the substrate. That the transition state structures of HIV-PR have not been identified makes a theoretical study of this kind particularly valuable for understanding the HIV-PR mechanism.