<p>This paper presents a two-stage optimization approach that involves linear integer programming models in each stage for determining optimal expansion alternatives for the Cape Floristic Region conservation areas in South Africa, with an emphasis on the protection of mammal species. While determining the optimal expansion areas, the following spatial and ecological criteria are taken into account: (i) a spatial connectivity of individual reserves, (ii) a minimum population of each species in each designated reserve, and (iii) an overall minimum population target for each species. We also aim for optimum economic efficiency by minimizing the total expansion area. The data set includes about 4000 candidate reserve sites and 38 species of large and medium-sized mammals. Empirical results indicate that the integer programming models can be solved without serious computational difficulty and the optimal reserve design provides substantial savings in financial resources.</p>