The clonal diversity of 105 Hemophilus isolates from the blood of children with lower respiratory tract infection in Pakistan was analyzed. Ten isolates were identified as H. parainfluenzae and 95 as H. influenzae. Of the H. influenzae isolates, 61 (64%) were serotype b and 34 (36%) were nontypable; 95% of the type b isolates were members of a single clonal group (as defined by multilocus enzyme electrophoresis, SDS-PAGE outer membrane protein profile, and biotype). This clone is rarely observed among type b strains recovered from patients with invasive type b disease in the USA or Europe. The nontypable isolates in Islamabad also were clonally restricted: 9 clonal groups were found among 34 isolates, with just 5 clonal groups accounting for most (82%) of the strains. Children infected with type b strains were hospitalized more often than those with nontypable H. influenzae disease (64% vs. 41%, P = .06), but no other clinical or demographic features distinguished children infected by type b and nontypable strains.