Blockade of neuromuscular activity during the period of naturally occurring cell death increases intramuscular nerve branching, synaptogenesis, and survival of embryonic chicken motoneurons. These results suggested that the enhanced motoneuron survival observed might result not from increased production of a trophic factor by the target, as often suggested, but rather from the enhanced ability of motoneurons to take up this factor via additional branches and/or synapses. Since removal of polysialic acid (PSA) by PSA-specific endoneuraminidase (endo N) during the period of nerve ingrowth and motoneuron cell death had been shown to reduce intramuscular nerve branching by altering adhesive interactions between axons and myotubes, we wished to determine, first, if this resulted in a reduction of synapse formation, and second, if this was correlated with decreased motoneuron survival. When PSA was removed from embryonic day 6 (E6) to E9 by injecting endo N into the limb, the number of synapses in the posterior iliotibialis muscle was greatly reduced both at E6.5, the onset of the cell death period, and at E7.5-E8, the middle of the cell death period. Total motoneuron counts at both E7.5-E8 and E10 (close to the end of cell death period) were significantly decreased compared to controls. These results indicate that a treatment that reduces intramuscular nerve branching and synapse formation also affects motoneuron survival. Furthermore, since removal of PSA in ovo via endo N altered neither the spontaneous embryonic motility nor the activation pattern of motoneurons or muscles, these experiments avoid the complication of activity blockade that may alter motoneuron survival by affecting events other than, or in addition to, intramuscular nerve branching.