The D.A.R.E. (Drug Abuse Resistance Education) program has relied on a curriculum that addresses a variety of psychosocial processes thought to be related to substance use and potentially modifiable through programmatic intervention. This study examines 12 postulated mediators of substance use prevention programs to determine the degree to which D.A.R.E. has an effect on mediators and the degree to which those effects account for behavioral outcomes of the program. Results indicate that the primary effect of D.A.R.E. is a change in commitment to not use substances. This change significantly mediates behavioral effects. However, the magnitude of D.A.R.E.'s effect on the mediator is relatively small. Other mediators that offer strong potential paths for intervention effectiveness are not affected by the program. These results suggest that in order to achieve prevention effectiveness, the curriculum used in the D.A.R.E. program needs to be replaced with one that targets and meaningfully changes appropriate mediating variables.