The diminished in vitro blastogenic response of lymphocytes from the elderly to mitogenic stimuli is cited as evidence of immunosenescence, but the response to specific microbial antigens has not been well characterized. We measured the response to tetanus toxoid before and after boosting in young and elderly subjects. Elderly subjects (age > or = 70) and young controls (age < 35) were subjected to clinical, laboratory, and nutritional evaluation to ensure a cohort of healthy subjects. Responses of lymphocytes from the elderly to the mitogens phytohemagglutinin and concanavalin A were markedly diminished compared to those from the young. For all subjects, the average in vitro blastogenic response to tetanus toxoid of lymphocytes from elderly subjects (n = 23) was significantly diminished compared to young controls (n = 23; 31,985 +/- 4502 vs 14,411 +/- 3714 cpm, p < .01). Following boosting with tetanus in those subjects in whom boosting with tetanus toxoid was indicated, blastogenesis was comparable between elderly (n = 17) and young subjects (n = 7; 38,078 +/- 11,451 vs 42,103 +/- 9247 cpm). The boosted response to tetanus apparently was not sustained, since in the subset of subjects with a history of tetanus immunization in the past 10 years, the response of the elderly was much less than that of the young. Thus, a cohort of healthy elderly with diminished blastogenic responses to mitogens was capable of at least a transiently normal response to tetanus post boosting.