One hundred three cases of bacteremia or meningitis due to Haemophilus influenzae in adults were evaluated. Among 96 episodes of bacteremia, 60% were due to pneumonia and 15% to genital-related infections; 10% had no apparent source of infection. Of 42 isolates serotyped in routine fashion by slide agglutination, 79% were reported as type b. In contrast, of 45 isolates from the same interval with confirmed serotyping (usually by counterimmunoelectrophoresis), only 29% were type b and 64% were nontypable; 26% had been misidentified by routine slide agglutination. The majority (85%) of confirmed typable strains were biotype I. Four (40%) of 10 nontypable obstetrical isolates belonged to the relatively rare biotype IV. Only 2% of isolates were ampicillin-resistant, despite a high resistance rate among pediatric isolates in the same communities. When serotyping is carefully performed, nontypable organisms appear to be the major cause of invasive H. influenzae disease in adults.