Haemophilus influenzae type b (Hib) invasive disease and oropharyngeal carriage continue in rural Alaska despite widespread vaccination. This study investigated whether invasive-disease reemergence during 1996-1997 could be attributed to strains distinguishable from strains carried by vaccinated children. Twenty-four invasive and 42 carriage Hib isolates, collected during 1992-1997, were characterized by pulsed-field gel electrophoresis (PFGE), multilocus enzyme electrophoresis, and biotyping. This Hib population was highly clonal, since only 2 strains, electrophoretic type (ET) 55/PFGE 1 and ET 56/PFGE 3, accounted for 62% of all isolates. The ET 55/PFGE 1 and ET 56/PFGE 3 strains were found in 74% of the carriers and caused 80% of the invasive Hib disease that occurred during April 1996-March 1997. Strains causing invasive disease could not be distinguished from strains carried by vaccinated children. Continued monitoring of Hib carriage may provide insights into the epidemiology of continued transmission in an era of widespread vaccination.