A quantitative evaluation of specific and nonspecific multiple unit activity (MUA) before and during pentylenetetrazol-induced EEG tonic-clonic discharges (OTCD) was made at four levels of the CNS: cortical, thalamic, mesencephalic, and pontine. In addition, MUA of sciatic nerve was recorded to detect possible spinal cord efferent discharges. At all levels, sustained increase in specific and nonspecific multiple unit activity preceded EEG and sciatic nerve discharges induced by pentylenetetrazol. Increments in nonspecific MUA occurred sooner and were larger than those of specific MUA, and increments in mesencephalic nonspecific MUA occurred sooner and were larger than those of other cortical, thalamic, and pontine nonspecific MUAs. This sequence of neuronal activation suggests that pentylenetetrazol seizures are initiated in nonspecific structures at the mesencephalic level.