This study was performed in order to establish whether selective depletion of somatostatin (SS) in the rat primary visual cortex obtained by cysteamine (CSH) administration results in changes of visual evoked potentials (VEPs). VEPs in response to a contrast reversal (0.5 Hz) of an optimal sinusoidal grating (0.1 cycle/deg, contrast 90%, mean luminance 15 cd/m2) were recorded from different layers of the binocular portion of the primary visual cortex of anesthetized rats with saline injection as well as before and after CSH treatment (90 mg/kg, s.c). VEPs of CSH treated rats, as compared to those obtained either in saline-injected animals or before drug administration, are reduced in amplitude at intermediate cortical layers whereas they are increased at deeper layers. VEP changes depend on CSH treatment and not on the extended anesthesia since no alterations in the VEP profile can be observed in saline-injected animals maintained in the same experimental condition. Forty-eight hours following CSH treatment, the VEP profile is comparable to that of saline-injected animals. Immunocytochemical analysis of the visual cortex of rats recorded 7 h after CSH treatment shows a 20–30% reduction in the number of SS-containing cortical cells. The highest reduction can be observed in cortical layer 5 although a significant decrease is also found in layers 2–3. In contrast, the pattern of SS immunoreactivity of the visual cortex of rats recorded 48 h after CSH administration is similar to that obtained in control conditions. These results indicate that a selective toxin for somatostatinergic systems induces a transient decrease of SS-containing cell number in selected cortical layers. Accordingly, CSH can serve as a useful pharmacological tool for the study of somatostatinergic function in the rat visual cortex since changes in VEPs can be related to a reduction of somatostatinergic neurons associated to CSH treatment. In particular, the present results suggest that one of the possible actions of somatostatinergic neurons in the rat visual cortex is to modulate the excitatory-inhibitory balance.