We studied the course of major mood disorders in the offspring of parents with well-characterised bipolar disorder prospectively for up to 15 years. All consenting offspring were assessed annually or anytime symptomatic. The participants began to develop major mood episodes in adolescence and not before. The index major mood episode was almost always depressive, as were the first few recurrences. Onsets and recurrences continued throughout the observation period into adulthood. We did not find evidence of pre-pubertal mania. In summary, adolescence marks the beginning of the high-risk period for major mood episodes related to bipolar disorder.