Ecología Austral, 24:83-93 (2014)Studies on the relationship between the richness of native and exotic plants have generated conflicting evidence depending, among others, on the spatial scale of analysis. This study assessed the invasion by exotic species in natural grasslands of Uruguay at a regional scale. We analyzed 313 vegetation census from four geomorphological regions: Cuesta Basaltica, Cuenca Sedimentaria, Centro Sur and Sierras del Este. The results showed that the relationship between native and exotic richness was negative for Centro Sur while the effect of native species richness on exotic plant cover was negative for Centro Sur and Cuenca Sedimentaria. In most analyses, the functional type C4 grasses was negatively associated with the exotic richness and cover, and strongly inhibits Cynodon dactylon, the only C4 exotic grass species present in the sites. Conversely, C3 species showed irregular patterns of association with the exotics. Also, exotic richness was positively related with the percentage of agricultural use and vegetation cover. Our results suggest that propagule pressure and productivity favour the introduction and establishment of exotic species, but they are largely controlled by the composition of the resident community, in particular by the presence of C4 perennial grasses, which are the group with the highest cover in these communities. This could explain the very low incidence of exotic species in Uruguayan grasslands.