The emergence of drug-resistant Streptococcus pneumoniae poses new clinical challenges and may also reflect a change in the epidemiology of S. pneumoniae infections. A variety of studies have shown that drug-resistant S. pneumoniae infections are linked to antimicrobial use. It has been hypothesized that persons of high socioeconomic status are at increased risk for a drug-resistant infection because of greater access to antimicrobial drugs. To assess whether median household income is associated with increased risk of penicillin-nonsusceptible S. pneumoniae infections, the authors geocoded and linked data from population-based surveillance for invasive pneumococcal disease with data from the 1990 US Census. Among invasive pneumococcal isolates from Atlanta, Georgia, in 1994, increasing proportions of penicillin-nonsusceptible isolates were associated with higher median household incomes (chi2 for trend, 15.17; p=0.002). Despite higher rates of invasive pneumococcal disease among blacks and persons who resided within lower median household income areas, white patients in areas with higher median household income had a higher risk of being infected with strains that were not susceptible to penicillin (Wilcoxon rank sum, Z=2.66, p=0.008). These findings demonstrated the utility of geocoding and US Census data in describing the epidemiology of drug-resistant S. pneumoniae and also provided more evidence that socioeconomic factors may influence the development of drug resistance.