After defining the receptive fields of single units in cortical area 17 of anesthetized cats, recurrent on-off stimulation with bars of light of optimal configuration win from a second micropipette; Progressively, three distinct alterations of neuronal activity developed. The most longlasting and usually the earliest abnormality was an increase in the number and frequency of spikes comprising a neuron's response to stimuli that were effective prior to iontophoresis. This enhanced physiologic response (EPR) could be elicited from a cell independently of the discharge activity of an induced focus, but only with stimuli appropriate for the cell's receptive field. With additional iontophoresis an entirely new response developed, which was consistent with an extracellular paroxysmal depolarization shift (PDS). This high-frequency burst of spikes appeared only in association with an ECoG interictal potential. It could be triggered, however, by stimuli which were previously effective or ineffective, as well as occur spontaneously. Characteristics which further distinguished the PDS from EPR included a longer and more-variable latency, a longer recovery period, and a different sensitivity to changes of stimulus intensity. A period of response inhibition also accompanied each interictal potential and persisted with a variable duration afterward. It was most noticeable as an interruption in the activity of tonically responding neurons and was often present before the cell began to generate PDSs. It was concluded that the EPR represents a direct effect of penicillin on the cell or its immediate synaptic connections, while the PDS appears dependent on the altered interactions within a population of such affected cells. The inhibitory phenomenon, in addition, seems a result of projected influences from cells more fully involved with the developing focus. A dynamic model of the EPR-PDS relationship is proposed.