The possible viral etiology of mumps-like illnesses in patients vaccinated for measles, mumps, and rubella (MMR) was studied by use of serum samples prospectively collected, during 1983-1998, from 601 acutely ill Finnish children and adolescents with mumps-like symptoms. Mumps virus was excluded by testing serum samples for mumps antibodies, and the serum samples were further tested for antibodies to adenovirus, enterovirus, Epstein-Barr virus, parainfluenza virus types 1-3, and parvovirus B19. The serum samples of 114 children <4 years old were also tested for antibodies to human herpesvirus 6 (HHV-6). A viral etiology was verified in 84 cases (14%), most commonly Epstein-Barr virus (7%), followed by parainfluenza virus types 1, 2, or 3 (4%) and adenovirus (3%). HHV-6 infection was found in 5 children <4 years old (4%). This study confirms that mumps-like symptoms in MMR-vaccinated children and adolescents are often not caused by mumps virus infection. Careful laboratory-based diagnostic testing of MMR-vaccinated children and adolescents who develop clinical symptoms compatible with those of mumps is important in the treatment of individual patients, in the comprehension of the true epidemiology of these illnesses, and in the evaluation of the impact of MMR vaccination programs.