In patients with focal epilepsy, EEG spike rate fluctuates considerably over time. We had previously shown that seizure occurrence played an important role in these fluctuations. We undertook this study to confirm this finding with better control of critical variables such as state of alertness and spike quantification, and to assess the spatial extent of the changes. Background activity changes and antiepileptic drug levels were also examined in relation to spiking. Spike discharge rate increased in the hours and days following seizures in widespread brain regions including, but not restricted to, the seizure focus. Spike rate did not change systematically before seizures. Postictal changes in background activity did not parallel spike fluctuations. Decreased antiepileptic drug levels did not cause increased spike rate. These results indicate that, following seizures, there is activation of interictal spiking which is not paralleled by changes in background activity. It is most often widespread and not necessarily most prominent at the site of seizure onset.