The protective effect of an experimental, inactivated Mycoplasma pneumoniae vaccine was evaluated by 1st injecting volunteers with vaccine and then infecting them with the organism. The vaccine induced the development of growth-Inhibiting antibody in 10 of 19 volunteers who Initially lacked this antibody. Following experimental challenge with M. pneumoniae, only one of 10 men who responded to the vaccine became ill, whereas, respiratory tract disease developed In 7 of 9 men who failed to respond to the vaccine and In 10 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.