We have recently shown in experimental nerve injury models that nerve regeneration is enhanced across a motor nerve graft as compared with a sensory nerve graft. To test the hypothesis that nerve architecture may mediate the beneficial effect of motor nerve grafting, we developed a model of disrupted nerve architecture in which motor and sensory nerve fragments were introduced into silicone conduits. Lewis rats were randomized to 5 experimental groups: nerve repair with motor nerve fragments, sensory nerve fragments, mixed nerve fragments, saline-filled conduit (negative control), or nerve isograft (positive control). At 6, 9, or 12 weeks, animals were sacrificed and nerve tissues were analyzed by quantitative histomorphometry. No significant differences were observed between the motor, sensory, and mixed nerve fragment groups. These findings suggest that intact nerve architecture, regardless of neurotrophic or biochemical factors, is a prerequisite for the beneficial effect of motor nerve grafting. © 2007 Wiley-Liss, Inc.