The purpose of this study was to estimate the prevalence of Neisseria meningitidis with decreased susceptibility to penicillin (MIC, >0.06 microg/mL) in North America (NA). Antimicrobial susceptibility testing by Etest (AB BIODISK, Solna, Sweden) was performed on 53 invasive clinical isolates obtained from 11 SENTRY Antimicrobial Surveillance Program participants in NA (9 states, 2 provinces) during 1998-99. All strains were markedly susceptible to ciprofloxacin (MIC(90), 0.008 microg/mL) and cefotaxime (MIC(90), < or = 0.002 microg/mL). Only 54.7% were susceptible to trimethoprim-sulfamethoxazole (TMP/SMX) at < or = 0.5/9.5 microg/mL. One strain was resistant to rifampin (MIC, > 32 microg/mL) and 16 isolates (30.2%) were relatively resistant to penicillin with MICs ranging from 0.094 to 0.25 microg/mL. No beta-lactamase production was detected. The serogroup distribution was 40% Y, 28% B, 24% C, 2% W-135, and 6% of strains were nongroupable. The prevalence of N. meningitidis with decreased susceptibility to penicillin in NA appears higher than previous reports.