Myoclonus associated with cyclic antidepressant therapy has been considered to be a rare phenomenon. Ninety-eight patients who were to begin receiving cyclic antidepressant therapy were prospectively evaluated for myoclonus. Thirty patients experienced clinically insignificant drug-associated myoclonus. Nine patients had clinically significant myoclonus. The myoclonus was reversible with the discontinuation of therapy but tended to persist if medication changes were not made. None of the tested clinical variables were able to predict which patients would develop myoclonus.