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The Regional Climate Change Index (RCCI) is employed to investigate hot-spots under 21st century global warming over Africa. The RCCI is calculated on 1-degree resolution grid from the ensemble of CMIP3 simulations for the A1B, A2 and B1 IPCC emission scenarios. The RCCI over Africa exhibits marked sub-regional variability. Seven sub-regions are identified over the area of investigation: Southern Mediterranean, Sahara, Western Africa, Eastern Africa, Equatorial Africa, Southern Equatorial Africa, and Southern Africa. Contributions from different factors to the RCCI are discussed for the sub-regions. Analysis of the temporal evolution of the hot-spots throughout the 21st century shows different speeds of response time to global warming for the different sub-regions. Hot-spots emerge in the Southern Mediterranean and Sahara. These hot-spots become evident by the mid of the 21st century and it is the most prominent by the end of the century. While hot-pots are generally evident in all the 7 sub-regions for the A2 scenario, in the A1B scenario, the hot-spots of Southern Mediterranean, Sahara, and South Africa emerge in the last 20 year period of the 21st century. No hot-spot emerge in the B1 scenario, which has the lowest GHG concentrations except for the Southern Mediterranean during the period 2061-2080. Our analysis indicates that sub-regional hot-spots show a rather complex spatial and temporal dependency on the GHG concentration and on the different factors contributing to the RCCI.