It has been suggested that adult attention-deficit/hyperactivity disorder (ADHD) may reflect affective temperaments, which involve mild manic and/or depressive traits as part of one’s personality. Such innate traits are associated with poor attention. Stimulant medications, given for ADHD, can worsen manic symptoms, thereby worsening attentional symptoms paradoxically, by worsening the underlying mood condition that causes poor attention. This study examines the nature of response to stimulant medication in subjects with affective temperament (Cyclothymia, Hyperthymia, Dysthymia). A retrospective cohort study was conducted of 87 subjects from Tufts Medical Center Mood Disorders Program. Subjects were included if they had ever been prescribed stimulant medications. Prior diagnosis of adult ADHD, or not, also was assessed. This sample was assessed using TEMPS-A scale to measure affective temperaments, and the CGI-I scale to assess clinical change in mood/anxiety and attention/cognition. Data analysis was conducted using descriptive statistics and stratification. This study has several limitations. Researchers and subjects were not blinded; all subjects received stimulants, with no non-stimulant control group; and treatment response was assessed retrospectively. Nonetheless, no such data exist in the scientific literature previously, and thus this pilot data adds to our present knowledge. 61% of the sample had an affective temperament (using the strictest definition of 75% or more TEMPS items endorsed). Of these, the most common was cyclothymic (40%) followed by hyperthymic (24%). The main treatment results were that most patients (55%) had no effect on mood/anxiety, but a large number (43%) had worsening mood/anxiety symptoms. 37% had mild or moderate improvement in cognition. Stratified by ADHD diagnosis, stimulant effects were somewhat better with, than without, ADHD diagnosis, for cognition but not for mood/anxiety. In ADHD subjects, 49% had worsening mood and/or anxiety symptoms, while 44% had some improvement in cognition/attention. In non-ADHD subjects, 30% had worsening mood and/or anxiety symptoms, while 30% had some improvement in cognition/attention. In conclusion, we found that most people (61%) treated with amphetamine stimulants identified in a mood specialty clinic were diagnosable with affective temperaments, especially cyclothymia. Amphetamine stimulant worsened mood/anxiety symptoms in about one-half of subjects, and improved cognition symptoms only about one-third subjects. Prior ADHD diagnosis was associated with somewhat improved cognitive, but not mood/anxiety, outcomes. These results suggest that amphetamine stimulant treatment in an affectively ill population may have harmful mood/anxiety effects, and has only partly beneficial cognitive effects.