This study examined whether prior regenerative growth through peripheral nerve (PN) bridging grafts influenced the specificity with which lesioned adult rat retinal ganglion cell (RGC) axons grew into co-grafts of developing target tissue (fetal superior colliculus). Growth into nontarget (muscle) tissue was also examined. Autologous PN was grafted onto the transected optic nerve. After 14 days, the distal ends of the PNs were placed next to, or inserted into, embryonic tectal tissue or into autologous muscle grafts placed in frontal cortex cavities. Host retinal projections were examined 3-8 months later using anterograde and retrograde tracing techniques. In rats in which there was good apposition between PN and tectal tissue, small numbers of RGC axons were observed growing into the tectal grafts (maximum distance of 180 Β΅m). No evidence of specific innervation of appropriate target regions within tectal grafts was detected, even though such regions (identified by acetylcholinesterase histochemistry) were often located close to the PN grafts. In rats with PN/muscle co-grafts, the extent of retinal axon outgrowth was greater (up to 465 Β΅m from the PN tip) and labelled profiles that resembled motor endplates were seen contacting muscle fibres. Previous studies have shown that spontaneously regenerating RGC axons consistently and selectively innervate appropriate target areas in fetal tectal tissue grafted directly into optic tract lesion cavities. Together, the data suggest that exposure to a PN environment may have reduced the extent of adult retinal axon growth into fetal tectal transplants and affected the way regenerating axons responded to specific developmental cues expressed by target cells in the co-grafted tissue.