In response to an increase in the incidence in invasive meningococcal disease (IMD) due to Neisseria meningitidis, a system of hospital- and laboratory-based surveillance was used in a prospective epidemiological and clinical assessment of IMD in children 0-13 years of age hospitalized in the Athens area between 1 January 1999 and 31 December 2000. The annual incidence of laboratory-confirmed disease was 10.2/100,000. Serogroup B strains were predominant. There was a sharp decrease in serogroup C from 19% of cases in 1999 to 3% in 2000 (P=0.013). Of note was the emergence of serogroup A responsible for 7% of the cases. The overall case fatality rate was 4.5%, but 2.8% for microbiologically confirmed cases. A remarkable decrease in disease severity assessed by admissions to intensive care units was noted during the second study year. Polymerase chain reaction-based methods for detection of meningococcal DNA were the sole positive laboratory test in 45% of the cases and the only test on which serogroup determination was based in 52% of groupable cases. The epidemiological and clinical profile of meningococcal disease appears to be rapidly evolving and close monitoring is required particularly for input into decisions regarding use of meningococcal vaccines.