A transient functional depression of thalamic activity (TFDTA) was induced in acute experiments in cats by the microinjection of 25% KCl into the thalamus. Spontaneous and evoked thalamic electrical activity was markedly depressed at the site of KCl microinjection. Spread of this depression to other thalamic areas often occurred, mainly when KCl was injected into the midline thalamus. In normal cats both spontaneous and evoked cortical spindle bursts as well as other evoked thalamocortical responses were reduced or abolished during the KCl-induced TFDTA. The generalized spike-and-wave discharges of feline generalized epilepsy were also suppressed for the duration of TFDTA, while incidental focal cortical interictal and ictal epileptic discharges, as well as generalized tonic-clonic seizure discharge, remained unaffected. The same effects were observed in animals with lesions of the mesencephalic reticular formation, indicating that the suppression of spindles and spike-and-wave discharges cannot be attributed to a release of the activity of the reticular formation by the TFDTA. An unexplained occurrence of generalized tonic-clonic EEG seizure was observed in most cases late after thalamic KCl microinjection, usually after the spike-and-wave discharges had recovered. These data are consistent with the hypothesis that the spontaneous bilaterally synchronous epileptic bursts of feline generalized penicillin epilepsy are not only closely related to spindles but are crucially dependent on thalamic inputs to the cerebral cortex.