Radiation Hybrid Mapping (RHM) provides a means of ordering markers on a chromosome. The process of mapping markers is equivalent to the traveling salesman problem, and thereby has combinatorial complexity. Addressing this computational complexity for a large number of markers is one problem addressed in the presented research. A related problem is that the quality of mapping information differs across markers. If unreliable markers are included in the mapping process, the overall accuracy of the map is decreased. A common approach to the latter or both problems is to start by building a framework map that only uses the most reliable markers. However, we will show that commonly used framework building techniques neither have the necessary chromosome coverage nor map quality, and most are prohibitively slow. The proposed approaches use a divide and conquer strategy that allows the mapping to be done more computationally efficiently, and that reduces the effect of unreliable markers on the map construction. Data from RHM of the human genome are used to test and evaluate the proposed approaches comparing the generated framework maps with physical maps and other framework maps. The proposed maps show good coverage of the chromosomes and high agreement with the physical map marker order.