We compared the distribution of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors and their individual subunits in synaptosomal and microsomal fractions prepared from 2-day-old (P2) and adult rat cortex. In P2 cortex more [3H]-(S)-fluorowillardiine ([3H]FW) binding to AMPA receptors was in the intracellular microsomal fraction than in the synaptosomal fraction whereas in adult rats the reverse was observed. Immunoblots with GluR1, GluR2/3, GluR4 and pan-AMPA antibodies showed the same profile. In contrast, the majority of [3H]MK-801 binding to the N-methyl-D-aspartate (NMDA) receptor and NR1 subunit immunoreactivity was present in the synaptosomal fraction at both developmental time points. These results suggest a developmental rearrangement of the distribution of AMPA receptors within neurons, a process which is likely to be important in synaptic stabilization and plasticity.