We report the reliability and validity of the Internal State Scale, a self-report instrument for the simultaneous assessment of severity of manic and depressive symptoms. The Internal State Scale consists of four empirically derived subscales: Activation, Well-Being, Perceived Conflict, and the Depression Index. All subscales had good internal consistency reliability. Activation subscale scores were significantly higher in manic patients than in depressed patients or control subjects, while Well-Being subscale scores were significantly lower and the Depression Index subscale scores were significantly higher in depressed patients than in the other two groups. Activation subscale scores were correlated specifically with clinician ratings of mania. Depression Index subscale scores were correlated specifically with clinician ratings of depression. Further evidence for the validity of the subscales of the Internal State Scale in reflecting manic or depressive symptoms came from discriminant function analysis in which these subscales assigned 88% of subjects to the correct diagnostic groups. In affectively ill patients who were studied in two or more mood states, Activation, Depression Index, and Well-Being subscale scores changed significantly in the predicted directions, while the same discriminant algorithm assigned 79% of mood states to the correct diagnostic category. Bimodal distribution of scores of manic patients on the Well-Being and Depression Index subscales substantiated earlier findings that euphoric mood is not an essential feature of mania. Based on findings from this and previous studies, the hypothesis is proposed that variables related to activation level, and not to mood state, constitute the core characteristics of the manic syndrome.