Since the earliest descriptions psychological and physical stress has been considered a controversial but potentially important factor in the onset and course of multiple sclerosis (MS). During recent years it has become clear that MS patients benefit from physical exercise as performed in aerobic training. As acute exercise has profound effects on immune and endocrine parameters we studied endocrine and immune response to standardized physical stress in MS within a study of aerobic training. Fifteen MS patients completed an eight-week aerobic training program, 13 patients were part of a wait-control group. Twenty healthy controls were recruited as well. A step-by-step bicycle ergometry was performed to determine individual exertion levels. For the endurance test patients exercised at 60% VO2 max for 30 min. Blood samples were drawn before, directly after and 30 min after completion of the exercise. Heart rate and lactate increased in all groups (p<.0001). We furthermore saw significant increases in endocrine parameters (epinephrine, norepinephrine, ACTH, and beta-endorphin; all p<.0001) in healthy individuals and in MS patients but without a differential effect. Whole-blood stimulated production of IFN-gamma (IFNgamma) was induced similarly in all groups (p<.01). TNF-alpha (TNFalpha) and IL-10 were less inducible in MS patients (trend). From these data we could not demonstrate a proinflammatory immune deviation in response to physical stress in MS. The observed trend of hyporesponsive TNFalpha and IL-10 responses in MS warrants further investigation.