Retinal and cortical lesions are completely different events that trigger visual cortical plasticity. We therefore compared the cortical effects of homonymous lesions of the central retina with effects of cortical lesions. All in vivo experiments were performed in anaesthetized, adult cats. Retinal lesions were made with a Xenon-light photocoagulator, and cortical lesions were induced by focal application of heat or ibotenic acid injection. Both, in cortical regions representing the retinal scotoma and at the border of small focal cortical lesions single neuron activity was initially suppressed and accompanied by a narrow area of increased activity adjacent to the region of functional loss during the first 1-2 weeks. At the same time an increased glutamatergic NMDA response and a reduction of GABA(A) and GABA(B) responses was observed around the cortical lesions in vitro. At an early stage long-term potentiation (LTP) is facilitated in those regions that were characterized by local upregulation of excitation and downregulation of inhibition after cortical lesions. Similarly, at the border of cortical scotomas in area 17 an increased glutamate level was found while inside the scotoma GAD levels were reduced. Shifts in topography of retinal representation as well as increases of receptive field size were detected as signs of lesion-induced neuronal reorganization after retinal and cortical lesions with longer survival times. A common cascade of events is triggered in the visual cortex by retinal as well as cortical lesions: reduced GABAergic inhibition and increased glutamatergic excitation, leading to increased spontaneous activity and visual excitability that is accompanied by facilitated LTP, and appears to initiate local cortical reorganization after functional disturbances in the visual system.