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Abstract The N-methyl-d-aspartate type glutamate receptor (NMDAR) is a molecular coincidence detector which converts correlated patterns of neuronal activity into cues for the structural and functional refinement of developing circuits in the brain. d-serine is an endogenous co-agonist of the NMDAR. We investigated the effects of potent enhancement of NMDAR-mediated currents by chronic administration of saturating levels of d-serine on the developing Xenopus retinotectal circuit. Chronic exposure to the NMDAR co-agonist d-serine resulted in structural and functional changes in the optic tectum. In immature tectal neurons, d-serine administration led to more compact and less dynamic tectal dendritic arbors, and increased synapse density. Calcium imaging to examine retinotopy of tectal neurons revealed that animals raised in d-serine had more compact visual receptive fields. These findings provide insight into how the availability of endogenous NMDAR co-agonists like d-serine at glutamatergic synapses can regulate the refinement of circuits in the developing brain.