Naturally acquired humoral immunity is thought to protect adults against serious infections due to Haemophilus influenzae type b (Hib). Antibody to the polyribosylribitol phosphate (PRP) capsule is generally considered protective; antibody to lipooligosaccharide (LOS) or outer membrane protein (OMP) may also play a role. Serum from 23 of 50 healthy young adults had no bactericidal effect (BE) against Hib yet opsonized these organisms for approximately 30% uptake by polymorphonuclear leukocytes. The degree of bactericidal and opsonizing activity in serum from the other 27 subjects generally correlated with the level of antibody to PRP but not to LOS or OMP. However, serum from some individuals had levels of antibody to PRP as high as 4.9 micrograms/ml without BE, and seven of 27 subjects with BE had antibody levels of less than 1 microgram/ml. After vaccination with 20 micrograms of conjugated PRP, the level of antibody to PRP was greater than 5 micrograms/ml in all 50 subjects. BE appeared in 22 of those who originally lacked it, and opsonization increased to approximately 50%.