The following hypotheses have been tested: (a) sensation seeking, A-State and Trait and Depressive Mood should positively affect the initiation and continuation of adolescent substance use: and (b) Following Zuckerman's conclusion with regard to the relationships between sensation seeking and drug use, and Khantzian's 'self medication hypothesis', different patterns of relationships between personality variables and substance use should be found: Whereas sensation seeking will be associated with substance use regardless of the specific psychopharmacological properties of a given substance, anxiety and depressive mood will be primarily associated with the use of depressants. One thousand nine hundred adolescents, 14-19 years old, were tested twice, 12 months apart, for alcohol and drug use. The major findings were as follows: (a) Sensation seeking was found to affect substance use among adolescents more than State and Trait Anxiety, and Depressive Mood; (b) Sensation seeking differentiated among abstainers, beginners, and users of all substances. A different pattern of relationship between State-Trait Anxiety, and Depressive Moods and substance use was found. These personality variables appeared to differentiate only among those subjects who used depressants; (c) It is also evident that previous experimentation with drugs significantly affect current-use. The implications of these findings for interventions among adolescents are discussed.