Streptococcus pneumoniae is a leading cause of morbidity and mortality in the United States, resulting each year in an estimated 3,000 cases of meningitis, 50,000 cases of bacteremia, 500,000 cases of pneumonia, and 7,000,000 cases of otitis media. As with most respiratory pathogens, rapid, sensitive, and specific diagnostic tests are not available; thus, early in the course of illness, diagnosis of S. pneumoniae infection is usually presumptive, and the choice of antimicrobial therapy is nearly always empiric. In the past, isolates of S. pneumoniae were uniformly susceptible to penicillin; however, penicillin-resistant and multidrug-resistant strains have begin to emerge in the United States and are widespread in some communities. The full impact of the problem is unknown because infection with drug-resistant S. pneumoniae (DRSP) is not a reportable condition for most of the United States. To develop a strategy for minimizing the impact of DRSP, in June 1994, CDC convened a working group of public health practitioners, clinical laboratorians, health-care providers, and representatives of key professional societies. This report describes the three goals developed by the working group that address surveillance, epidemiologic investigation, and prevention and control of DRSP, and the objectives for each goal.