The authors used a systematic life-chart methodology to observe four patients with bipolar disorder in whom long periods (6-15 years) of effective lithium prophylaxis were followed by relapses on lithium discontinuation. Once the drug was reinstituted, it was no longer effective. The incidence, predictors, and mechanisms underlying this phenomenon all require further systematic study. The current preliminary observations suggest an additional reason for caution when lithium discontinuation in the well-maintained patient is considered.