Sudden unexplained death in epilepsy occurs when epilepsy patients die suddenly and unexpectedly in the absence of recent tonic-clonic seizure activity. There is currently no known reliable indicator of acutely lethal seizure activity. Clinical studies record a relationship between recent (within 10–40 minutes) seizure activity and elevated serum prolactin levels, and postictal elevation of prolactin within peripheral vessels has proved clinically useful in determining recent seizure activity. The authors hypothesized that elevated prolactin could be detected in cerebral vessels by immunohistochemical stains, serving as a marker for sudden unexplained death in epilepsy. They conducted a retrospective study of individuals who died in their jurisdiction during the 14 years from 1986 through 1999. The study contained one group of individuals who died of sudden unexplained death in epilepsy, a group with epilepsy who died of some other cause, and a control group whose members died rapidly of a gunshot wound of the torso. Sections of hippocampus and neocortex were obtained and stained with a polyclonal prolactin antibody. No significant difference in the level of immunostaining for prolactin in cerebral vessels was found between the experimental and control groups. A review of the protocols used indicates that revision of certain aspects may provide better immunostaining and more conclusive results.