Most persons who receive hepatitis B vaccine during infancy will have a level of antibody to hepatitis B surface antigen (anti-HBsAg) of <10 IU/liter 10 to 15 years later; however, most will demonstrate immune memory by an anamnestic response to a vaccine challenge dose. To determine whether there was a difference in anamnestic response among college students vaccinated during infancy, we compared anti-HBsAg levels after a 20-μg dose of Engerix-B in those with a residual anti-HBsAg level of 0 IU/liter and those with levels of 1 to 9 IU/liter. Anti-HBsAg was measured before (baseline) and 2 weeks after a challenge dose; a response was defined as a level of ≥10 IU/liter after the dose among those with <10 IU/liter at the baseline. Of the 153 students who completed the study, 130 (85%) had an anti-HBsAg level of <10 IU/liter at the baseline, 72 had a level of 0 IU/liter, and 58 had levels ranging from 1 to 9 IU/liter. Students with a levels of 1 to 9 IU/liter were more likely to respond to the challenge dose than those with a baseline anti-HBsAg level of 0 IU/liter (83% versus 50%; P < 0.001). The presence of any detectable anti-HBsAg among persons vaccinated in the remote past may indicate the persistence of immune memory.