We recently saw two unusual manifestations of Haemophilus influenzae infection in adults in the Seattle area: fulminant sepsis in an otherwise-healthy man and three episodes of bacteremia in a woman with chronic liver disease. We retrospectively identified 79 bacteremic and 40 non-bacteremic cases of invasive H. influenzae infection developing in patients > or = 9 years of age between 1 January 1980 and 31 December 1990. The most common clinical presentations among patients with bacteremia included pneumonia (52%), septicemia (27%), meningitis (8%), gynecologic infection (5%), and epiglottitis (5%). Underlying illnesses were common in these patients, and overall mortality was 35.5%. Factors associated with mortality included underlying neurological disease, polymicrobial bacteremia, and advanced age. The clinical presentations of the 40 patients without bacteremia included soft-tissue abscesses (45%), lung abscesses (18%), peritonitis (13%), meningitis (8%), gynecologic infection (8%), epididymitis (5%), mastoiditis (3%), and osteomyelitis (3%). Thus H. influenzae disease has a variety of presentations and is associated with significant mortality in older children and adults. Further study is required to determine whether widespread administration of H. influenzae type b conjugate vaccine to infants will alter the development of subsequent disease in later life.