Study objective: To determine what change, if any, occurs in the serum anticapsular antibody concentration immediately after immunization with either Haemophilus influenzae type b capsular polysaccharide vaccine (PRP) or a vaccine consisting of the capsular polysaccharide conjugated to diphtheria toxoid (PRP-D). Setting and patients: Children: a convenience sample of 32 healthy 2-year-old children from diverse locales. Adults: a convenience sample of 16 healthy adults chosen from employees at the Washington University and Tulane University schools of medicine. Interventions: PRP or PRP-D vaccine administered to the adults and serum obtained daily for 5 days. PRP vaccine was administered to the children, and serum was sampled 2 or 3 days or 4 or 5 days after immunization, or both. Measurements and main results: Decline in serum antibody in all seven (100%) adult recipients of PRP. The nadir occurred on days 1 to 3, and the decrease average 26.0% of the preimmunization concentration. Eight (89%) of nine PRP-D recipients had a similar decline that averaged 25.9%. Of 29 children, 20 (69%) had a decline that averaged 14.7%. The magnitude of anticapsular antibody present before immunization was correlated with the magnitude of the observed decrease. Conclusions: A decrease in serum antcapsular antibody occurs in most children and adults immunized with PRP (adults and children) or PRP-D (adults). Such a decrease might transiently increase the risk of invasive disease if it occurred during a period of asymptomatic colonization with H. influenzae type b.