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Objective: Antidepressants have been associated with the induction of mania and rapid cycling. This study examined whether antidepressant-associated manic states differ in any way from spontaneous mania. Method: Forty-nine consecutive inpatients with antidepressant-associated manic states were compared with 49 matched inpatients with spontaneous mania in a blind, retrospective chart review. Results: Across virtually every clinical measure examined, the patients with antidepressant-associated manic states experienced milder and more time-limited manic episodes than the patients with spontaneous mania. The patients with antidepressant-associated manic states were subject to frequent checking by nurses and hall restriction for a significantly shorter period of time than the patients with spontaneous mania. The patients with antidepressant-associated manic states also had significantly less severe levels of delusions, hallucinations, psychomotor agitation, and bizarre behavior, according to a standard rating instrument, than the patients with spontaneous mania. For further study the patients with antidepressant-associated mania were divided into subgroups taking four individual classes of antidepressant drugs: tricyclics (N=19), fluoxetine (N=13), monoamine oxidase inhibitors (MAOIs) (N=8), and bupropion (N=6); three patients taking combinations of drugs were not included in these analyses. The patients with MAOI- and bupropion-associated mania had a slightly lower overall rating of severity of psychopathology at admission than the subgroups with fluoxetine- and tricyclic-associated mania. Conclusions: Antidepressant-associated mania appears to be a milder and more time-limited syndrome than spontaneous mania and may represent a distinct clinical entity. MAOIs and bupropion may be associated with milder manic states than either tricyclic drugs or fluoxetine.