In 3 different models of opioid epileptogenesis we have utilized opioid receptor antagonists to differentiate the nature and role of opioid receptor subtypes involved in opioid agonist-induced epileptoid responses in rats. Selective mu-opioid receptor agonism can initiate epileptoid responses in non-dependent rats. Delta-opioid agonism is important in sustaining mu-initiated epileptoid responses. A role for mu-opioid receptor stimulation in delta-opioid initiated epileptoid responses remains yet to be clarified. Delta-opioid antagonism does not precipitate classic autonomic and behavioral signs of withdrawal in morphine-dependent rats but blocks epileptoid responses in naloxone-precipitated morphine withdrawal without affecting autonomic and behavioral components of an ongoing withdrawal reaction.