We have investigated the effect of intracranial injections of the amnestic anti-metabolite, 2-deoxygalactose, and antibodies to the neural cell adhesion molecule on retention of a one-trial passive avoidance task in chicks. Groups of chicks received bilateral intracranial injections of 10 mumol/hemisphere 2-deoxygalactose or 10 microliters/hemisphere anti-neural cell adhesion molecule and were tested 24 h following training. 2-Deoxygalactose injections were amnestic when administered at a previously established time (30 min pre-training). Here we show that the agent is also amnestic when injected within a second time window occurring specifically 6-8 h after training. Administration of 2-deoxygalactose between 2 and 6 h or after 8 h post-training was without effect on retention tested 24 h following training. Anti-neural cell adhesion molecule injections were amnestic only when performed at a time which coincided with the second phase of 2-deoxygalactose susceptibility. Further experiments demonstrated that the neural cell adhesion molecule is one of the molecules into which 2-deoxygalactose is incorporated. Additionally, we investigated the extent of diffusion of 2-deoxygalactose and anti-neural cell adhesion molecule following their injection, with respect to their residence in forebrain loci known to be involved in the memory for passive avoidance. We interpret these data as indicating that two waves of glycoprotein synthesis are necessary for the establishment of long-term memory for the experience of passive avoidance training. The evidence is discussed in the context of earlier results indicating that the two waves involve different glycoprotein species and, possibly, different forebrain regions. We speculate that the late phase of glycoprotein synthesis coincides with, and is required for, modulation of cell-cell adhesion processes, reflecting the selection and stabilization of synapses which maintain an enduring representation of long-term memory.