The authors previously reported the results of an investigation into the potential of inoculation to promote resistance to smoking onset in young adolescents. Inoculation videos were administered to 1,047 adolescents in a midwestern city. Results for the first year indicated that inoculation promotes resistance to smoking initiation but only among adolescents of low self-esteem. This report follows up the first-year results in an effort to assess the permanence of the initial effects. The results during the second year revealed main effects for inoculation on attitudes, suggesting modest persistence for the initial pretreatments, and a weak interaction effect in the fall, which dissipated by spring. In addition, the pattern of results suggests that if resistance approaches are to have a chance of success in smoking prevention they must target young adolescents at the point of transition from primary (elementary) to secondary (middle or junior high) school. Beyond this pivotal juncture, adolescents’attitudes opposing smoking quickly deteriorate, therefore rendering the resistance paradigm inappropriate.