Measles has been a major killer among vaccine-preventable diseases in children < 5 years of age in developing countries. Despite progress in global efforts to reduce mortality, measles remains a public health problem. Hospital-based measles surveillance was conducted in Manhica, Mozambique (July 2001–September 2004). Suspected cases and community-based controls were enrolled, and blood was collected for immunoglobulin M (IgM) confirmation. Two hundred fifty-three suspected cases and 477 controls were enrolled, with 85% (216 of 253) cases reported during a measles outbreak. Measles-IgM confirmation was 30% among suspected cases and 5% in controls. Fifty-eight percent (14 of 24) of laboratory-confirmed cases had records indicating previous measles vaccination. Mortality was 3% (8 of 246) among cases and 1% among controls (6 of 426). Forty-five percent (33 of 74) of cases were < 24 months of age and 22% occurred in infants < 9 months of age and were associated with a high case-fatality rate (25%). Our data suggest that improved diagnostics, new tools to protect infants < 9 months of age, and a supplemental dose of measles vaccine could assist measles control.