Following the death of 2 adolescents due to serogroup C invasive meningococcal disease (SCIMD) in April 2008, the Chicago Department of Public Health (CDPH) observed a high level of concern in 2 Chicago communities inferred to have low meningococcal vaccine (MCV) coverage rates. In response, CDPH promptly mobilized additional resources, administering 5,343 doses of MCV in 40 schools over 2 weeks and immunizing 44% of enrolled students aged 11 to 18 years. The number of eligible students vaccinated per school ranged from 9 to 466 (median, 112) and the proportion of age-eligible students receiving the vaccine ranged from 5% to 87% (median, 52%). The attributes of the SCIMD activity did not meet the definition of a community-based outbreak, but presented an opportunity to promptly intensify existing mechanisms for meningococcal vaccination of adolescents in the affected neighborhoods and overcome traditional barriers to vaccination.