The maturation of short-term synaptic plasticity was studied in slices of the visual cortex obtained from rats during the first 47 days of postnatal life. Responses of cortical neurons to repetitive stimulation of the white matter at frequencies >5 Hz were examined by recording intracellularly at the resting membrane potential level. Paired-pulse facilitation, an increase in the excitatory intracellular response following an initial response, was present in approximately 40% of the neurons studied from postnatal day 5 (P5) to P10. Most of the remaining neurons studied at these ages did not reveal paired-pulse interactions. There was a progressive, age-related increase in the proportion of cells displaying paired-pulse depression, a decrease in the second excitatory response relative to the first, and a concomitant decrease in the proportion of cells displaying paired-pulse facilitation. Thus, at P31-P47 approximately half of the neurons revealed depression of synaptic transmission following an initial stimulus, while most of the other neurons displayed a lack of temporal interactions. At these later ages, inhibitory potentials also displayed paired-pulse interactions. Maturation of paired-pulse depression of the excitatory response is temporally correlated with the development of intracortical inhibitory mechanisms and may reflect subtractive or shunting inhibition in the postsynaptic neuron as well as presynaptic inhibitory mechanisms. Consistent with a role of GAGAergic inhibition, application of GABA receptor antagonists produced reversible blockade of paired-pulse depression. In conclusion, cortical neurons display substantial maturation in short-term synaptic plasticity during the first postnatal month. Temporal facilitation may be important in enhancing excitatory neurotransmission at a time when synapses are very immature. In the mature cortex, suppressive temporal interactions could provide an important substrate for neuronal processing of visual information.