A syndrome of red eyes and respiratory symptoms was noted following receipt of influenza vaccine in Canada during the 2000-2001 influenza season. We conducted intra-dermal skin testing to determine if oculo-respiratory syndrome (ORS) was related to failure of the splitting process during vaccine manufacturing, if it was associated with a particular viral strain and to identify individuals at risk for subsequent ORS reaction. Skin testing with minute quantities of vaccine antigen induced ORS symptoms at a higher rate amongst persons previously affected by this syndrome compared to previously unaffected persons. Skin test reaction size or quality could not identify persons at risk of ORS. Skin testing could not identify a specific strain or the stage in the manufacturing process during which the trigger may have been introduced.