The one-and-a-half dimension multilayer Lagrangian model LATOX was developed to model the environmental pollution of deep stratified lakes and semi-enclosed seas. This model is used to simulate changes in the system of the Mediterranean seas, forced by the changes of climate and anthropogenic factors. It incorporates the submodels of the Black Sea, Azov Sea, Marmara Sea and the western and eastern Mediterranean. Simple submodels of the Kerch, Bosphorus, Dardanelles, Sicily and Gibraltar straits are applied. Three case studies were carried out: (i) the reconstruction and prediction of the 137Cs contamination from testing of nuclear weapons and the Chernobyl accident, (ii) the prediction of possible changes in the Azov and Black seas under increased freshwater consumption and (iii) the evolution of the Black and Azov seas to their recent state over the last 7000 years. The reconstruction of the 137Cs was quite good, and the model predicted a return to pre-Chernobyl level by 2010, in the absence of future accidents. An increase of freshwater consumption in the Black Sea basin catchments to 100 km3/year can cause significant changes to the Black and Azov seas.