Microglia, which are the resident macrophages of the brain, have an important role in the elimination of synapses during brain maturation, a process known as 'synaptic pruning'. This study proposes that a deficiency in microglia can contribute to defective neurodevelopment and neuropsychiatric disorders. Mice lacking the receptor for the neuron-derived CX3C-chemokine ligand 1 (also known as fractalkine) exhibited a transient reduction in microglial cell numbers during the early postnatal period. This resulted in an early reduction in synaptic pruning, which persisted into adulthood, and was associated with an increased number of synapses but reduced synaptic transmission, as well as with anti-social behaviour. This suggests that microglia are important for brain homeostasis as they maintain optimal synapse density and have a role in brain wiring and behaviour.