Two doses of inactivated Mycoplasma pneumoniae vaccine were administered 77 days apart to 12 antibody-negative and six antibody-positive children. Few or no rises in CF or growth-inhibiting antibody were detected in the 12 subjects who were initially antibody-negative, and minimal increases were observed in children with preexisting antibody. Peripheral lymphocytes obtained before immunization from antibody-negative children were not stimulated by M. pneumoniae antigen in vitro, but five of the six immune subjects had reactive lymphocytes. Antigenreactive lymphocytes appeared in 58% of the antibody negatives after the first inoculation and in 91% after the booster dose. These data suggest that inactivated M. pneumoniae vaccine may be inadequate for primary immunization; rises in antibody, when elicited, may be due to anamnestic stimulation of naturally acquired immunity. Sensitization of lymphocytes, in the absence of production of antibody, has not been reported previously, and its significance in these and other recipients of killed vaccines is unknown.