Gender differences reported in nociceptive and nerve injury research should be considered before conclusions about basic pathologic mechanisms are drawn. Holtzman male rats are routinely used in the mononeuropathy model produced by a peripheral nerve freeze lesion, sciatic cryoneurolysis (SCN). SCN reproducibly results in abnormal behaviors which include autotomy, the gnawing and scratching of the affected hindpaw. In the present studies, the incidence and severity of autotomy 1 to 21 days following SCN was compared in male and female Holtzman rats. Female Holtzman rats displayed a decreased incidence and severity of autotomy 7 days and beyond following SCN. This disparity was statistically different at 14 days (p < 0.01) and at 21 days (p < 0.05) by Newman-Keuls test. Morphometric comparison of the sciatic nerve at the lesion site in male and female rats 14 days post-SCN (time of peak autotomy behavior in this model) displayed differences in the fascicular percentage of edema (p < 0.01) and remyelinating axons (p < 0.05) between genders using Student's t-test. However, these percentage values did not correlate with either the incidence or severity of autotomy scores for those animals. Therefore, biochemical differences at and/or proximal to the peripheral nerve freeze lesion may be responsible for mechanisms which generate or relate to autotomy.