The present study aimed at investigating to what extent the regulation of excitability in cortical networks, as indicated by surface-negative slow cortical potentials (SCPs), is impaired in epileptic patients and to what extent training of SCP self-regulation by means of biofeedback and instrumental learning procedures might affect seizure frequency. Twenty-five patients suffering from drug-refractory epilepsies (complex focal, grand mal, and absence type of seizures) participated in 28 1-h sessions of feedback and instrumental conditioning of their SCPs. Subjects' EEGs were obtained from the vertex. Depending on discriminative stimuli DC shifts towards increased or suppressed negativity relative to the pre-trial baseline were demonstrated by on-line visual feedback during intervals of 8 s each; each session comprised 110 trials. While performance on the SCP self-regulation task was initially below normal (as compared to healthy subjects), significant increases in SCP control were achieved by the patients across the 28 training sessions. In 18 patients at least 1-year follow-up data are available. Changes in seizure frequency were related to transfer of SCP control with six of the patients becoming seizure-free. Age affected the ability to acquire SCP control and its impact on seizure frequency.