The sciatic nerve of rats and cats is commonly used in experimental models of peripheral nerve injury and repair, as well as experiments involving peripheral nerve electrode implantation. In such experiments, morphometric parameters from the implanted nerve are commonly evaluated and compared to control values obtained from the contralateral nerves. However, this may not be an appropriate approach as differences may naturally exist in the structure of the two nerves owing to developmental or behavioral asymmetry. Additionally, in the cat, baseline values for standard morphometric parameters are not well established. In this study, we characterized fascicle area, fiber count, fiber density, fiber packing, mean g-ratio, and fiber diameter distributions in the rat and cat, as well as investigated the potential for naturally occurring sided differences in these parameters in both species. We also investigated whether animal age or location along the nerve influenced these parameters. We found that sided or left/right leg differences exist in some parameters in both the rat and the cat, calling into question the validity of using the contralateral nerve as a control. We also found that animal age and location along the nerve can make significant differences in the parameters tested, establishing the importance of using control nerves from age-and behaviorally matched animals whose morphometric parameters are collected and compared from the same location. Anat Rec, 298:1492Rec, 298: -1501Rec, 298: , 2015. V C 2015 Wiley Periodicals, Inc.