In a partial replication of the Harlow, Newcomb, & Bentler (1986) study, the relationships between depression, meaninglessness, suicide ideation, and substance abuse are examined in two samples of adolescents (48 high school students and 113 patients in two psychiatric hospitals). Correlational analyses indicated that the high school students who viewed themselves negatively, were depressed, or who had found little meaning in their lives were more likely to consider suicide and to abuse drugs. Regression and structural modeling analyses uncovered a strong mediational relationship between purpose in life with the precursor of depression and the consequent of substance abuse.