The present invention provides CTLA-4 monoclonal antibodies, particularlyhumanized monoclonal antibodies specificallybinding to CTLA-4 with high affinity. The present invention also providesfunctional monoclonal antibodies cross-reactive toCTLA-4 of human, cynomolgus monkey and mouse. The present invention furtherprovides amino acid sequences of the antibodiesof the invention, cloning or expression vectors, host cells and methods forexpressing or isolating the antibodies. The epitopes of theantibodies are identified. Therapeutic compositions comprising the antibodiesof the invention are also provided. The invention alsoprovides methods for treating cancers and other diseases with anti-CTLA-4antibodies.