The ability of retinal tissue to propagate "spreading depressions" (rSDs) depends on the endogenous properties of the tissue and requires an intact neuro-glial network. The phenomenon of rSDs, therefore, may be used as a tool to assess the functional integrity of brain tissue. We interfered with transmembranal Cl- movements in order to characterise the reactivity of the neuro-glial network subsequent to a pharmacological treatment. The rSDs were monitored by means of double-barrelled microelectrodes for de and extracellular Cl- recordings using the in vitro model of circling spreading depressions in the chicken retina. The application of the Cl-/HCO3-; exchange inhibitor DNDS caused the rSD related amplitude of the de signal as well as that of the Cl- signal to decrease until the point that rSDs finally ceased. The drug-induced changes of the de potential as well as those of the Cl- signal occurred in close correlation. This suggests that rSD related Cl- transients are an intrinsic property of de generating mechanisms. The data also show that modulation of only one of several possible mechanisms involved in the regulation of Cl- homeostasis as eg by DNDS is sufficient to prevent propagation of rSDs. Since propagation of rSDs requires the interaction of several excitatory and inhibitory processes, the present experiments indicate that the retinal tissue was made less susceptible to hyperexcitation by blocking the Cl-/HCO3-; exchanger with DNDS. Thus, Cl- exchange mechanisms seem to play a more important role in maintaining cellular excitability than taken into account so far.