The protective effect of an experimental, inactivatedMycoplasma pneumoniaevaccine was evaluated by first injecting volunteers with vaccine and then infecting them with the organism. The vaccine induced the development of growth-inhibiting antibody in ten of 19 volunteers who initially lacked this antibody. Following experimental challenge withM pneumoniae,only one of these ten men who responded to the vaccine became ill, whereas, respiratory tract disease developed in seven of nine men who failed to respond to the vaccine and in ten of 13 volunteers in the control group who lacked the antibody. The most severe clinical illnesses developed in the men who failed to respond to the vaccine. These findings suggest that the vaccine had a protective effect in those men who developed antibody, while those who failed to develop antibody may have been sensitized.