Synaptic depression was assessed from intracellular recordings in cortical tissue slices. Evoked postsynaptic potentials exhibited synaptic depression with an exponential or double exponential decrease (time constants: < 1-30 s) in amplitude during repetitive afferent stimulation by short trains of suprathreshold stimuli. Depressed synaptic responses with an exponential time course (time constants: 10 s-8 min) during presentation of similar short trains of stimuli every 5 or 10 s. Cortical cells recorded extracellularly in cat visual cortex show similar time constants of response decrement during adaptation to moving stripes. Postsynaptic voltage- or ion-regulated conductances and chloride conductances do not appear to be involved in synaptic depression. Input resistance changes and effects of injection of chloride indicate a lack of GABAA receptor-mediated effects. Hyperpolarizing or depolarizing neurons, and pairing polarization with afferent stimulation, also did not affect synaptic depression. This distinguishes these processes from long-term depression and long-term potentiation. Our results suggest that the most likely mechanisms of synaptic depression and adaptation in cortical cells are presynaptic decrease in transmitter release and/or receptor desensitization. Short-term postsynaptic changes may also occur after synaptic depression.