Platelet monoamine oxidase (MAO) activity is a peripheral marker of central serotonergic activity, and has been associated with aggressive, impulsive and hyperactive behaviour, alcohol and drug abuse. Central serotonergic activity has also been associated with plasma cholesterol levels. In the present longitudinal investigation in adolescents (n = 320) changes in platelet MAO activity and in plasma cholesterol levels over three years were measured, and their possible association with changes in aggressive and hyperactive behaviour, smoking, alcohol and drug use was studied. The measures were taken at age 15 and 18 years. Psychological data were obtained from teachers by using the Hyperactivity Scale [B. af Klinteberg, Studies on Sex-related Psychological and Biological Indicators of Psychosocial Vulnerability: A Developmental Perspective, University of Stockholm, Department of Psychology, 1988]. The results of the study show that in most of the tested individuals, platelet MAO activity is a relatively stable measure, however, there was a significant number of subjects with a noticeable change in MAO activity. In subjects with decreased platelet MAO activity, total and HDL cholesterol levels were significantly increased. Also, changes in HDL cholesterol and in platelet MAO activity were inversely associated with changes in the score of Concentration Difficulties. The changes in platelet MAO activity and cholesterol level were not associated with alcohol and drug use among the subjects. This longitudinal analysis provides preliminary evidence that changes in platelet MAO activity and cholesterol, which may reflect changes in central serotonergic activity are associated with attention deficit in adolescents.