The authors conducted a prospective and descriptive pilot study in 14 healthy medical students, investigating whether a psychologically stressful event (final examination) may modify serum tumor necrosis factor alpha (TNF-alpha) levels. There was a dramatic and sustained decrease of phytohemagglutinin (PHA)-induced TNF-alpha several weeks before and the day of the examination, followed by a significant increase of TNF-alpha starting the next day. Examination-induced stress was confirmed by both elevated urinary cortisol concentration and significant increase in stress scale scores. Extending these results to patients suffering from multiple sclerosis (MS) leads to the hypothesis that psychological stress may influence the course of MS by substantially altering TNF-alpha levels, and suggests the need for further studies in MS patients exposed to stressful conditions.