Antimicrobial susceptibility, pneumococcal surface protein A (PspA) serotyping, and pulsed-field gel electrophoresis (PFGE) were used to evaluate clonal relatedness among 66 invasive isolates of Streptococcus pneumoniae serotype 6B collected during 1982-1996 from patients in Alaska. Thirty-seven (56%) of the isolates had penicillin minimal inhibitory concentration values >/=0.125 microgram/mL and were resistant to at least 1 other antibiotic. Fourteen PspA serotypes were observed; PspA 16 was the most common (35%). Forty-five (68%) of the 66 isolates shared common and highly related PFGE patterns using 3 enzymes. Twenty-six (58%) of the isolates with common PFGE patterns were from Native Alaskan children </=2 years of age residing in 1 region of Alaska. Alaskan serotype 6B had distinct PFGE patterns, compared with the South African 6B-8 and Spanish 6B-2 multidrug-resistant clones, suggesting that the Alaskan 6B isolates were distinct from these other pneumococcal 6B clones but were genetically related to each other [corrected].