Wide geographic variation in the prevalence of drug-resistant Streptococcus pneumoniae demonstrates the importance of tracking antimicrobial resistance locally. This survey of hospital microbiology laboratories in New York City found that penicillin resistance (MIC > or = 2.0 micrograms/ml) increased from 1.5% of S. pneumoniae isolates in 1993 to 6.3% in 1995 and that in 1995, one-third of isolates nonsusceptible to penicillin (MIC > or = 0.1 microgram/ml) were also nonsusceptible to an extended-spectrum cephalosporin (MIC > or = 1 microgram/ml).