Emergence of drug-resistant Streptococcus pneumoniae (DRSP) presents a challenge to the medical and public health communities since the magnitude of the problem is not known, the clinical impact of DRSP infections is not well described, national vaccination rates are low, and antimicrobial drugs are often used excessively and inappropriately. To address the problem of DRSP, a working group sponsored by Centers for Disease Control and Prevention was formed in June 1994 consisting of public health practitioners, health care providers, and clinical laboratorians representing state and federal agencies and various professional organizations. Through periodic open meetings, the working group has developed a strategy for surveillance, investigation, prevention, and control of infections due to DRSP. The strategy focuses on (1) implementing an electronic laboratory-based surveillance (ELBS) system for reporting invasive DRSP infections and providing clinically relevant feedback to clinicians, (2) identifying risk factors and outcomes of DRSP infection, (3) increasing pneumococcal vaccination, and (4) promoting judicious antimicrobial drug use. Data received through ELBS will be used to make timely estimates of the community-specific prevalence of drug-resistant pneumococci. National, regional, and local trends will be made available to health care providers and clinicians to promote optimal antimicrobial drug use and increased vaccination in targeted areas. Once in operation, the ELBS network will be adaptable to other diseases, improving the comprehensiveness and timeliness of public health surveillance. The intended outcome of the strategy is to reduce complications of DRSP infection, such as long-term sequelae of infection, health care expenditures, morbidity, and mortality.