In this study in the Islamic Republic of Iran 365 measles cases were evaluated to distinguish between primary infection with measles and reinfection due to secondary vaccine failure. All cases previously confirmed by detection of specific IgM were tested for IgG avidity. A secondary immune response was seen in 18.4% of patients. All unvaccinated patients (16.7%) showed a primary immune response. Of 244 patients with documented vaccination, 75.8% showed a primary immune response and 24.2% showed a secondary immune response, thereby indicating a secondary vaccine failure. Almost all measles reinfections (99%) were seen in patients >10 years old, indicating that vaccination for 10-year-old children is recommended.