The purpose of this study was to identify the optimal murine model for the study of peripheral nerve injury and nerve and limb transplantation. The degree of self-mutilation (autotomy) following sciatic and saphenous nerve injury was assessed in four mouse strains, Balb/C, C57BL/6J, C57BL/10J, and C3HEB, commonly used in surgical research. Experimental groups included sciatic and saphenous nerve transection with repair (n = 9) or without repair (n = 9), as well as housing arrangements favoring social interaction vs. isolation. Autotomy was most prevalent in the Balb/c and C3H strains at 56% and 89% overall, respectively, and was much less frequently seen in the C57BI/10 and C57BI/6 strains (22% and 11%, respectively). Autotomy was found to correlate most strongly with mouse strain, and with social contact as well. Two strains, C57BL/6J and C57BL/10J, were found to be highly resistant to self-mutilation, and are thus ideal animal models for peripheral-nerve and whole-limb transplant studies.