Research on the causes of psychological distress in women in midlife has focused on current adversity and hormonal changes associated with menopause and paid less attention to possible risk factors across the life course. We examined the factors in childhood, adolescence and earlier adult life that show persisting effects on psychological symptoms reported annually over a 6 year period (47-52 years) using prospective data on a cohort of 1500 British women who have been followed since their birth in 1946. Even after taking into account the powerful effect of recent life stress, this study found that women with a high level of psychological distress had different life course trajectories than those with less distress. They were more likely to have scored highly on the neuroticism scale or exhibited antisocial behaviour when they were teenagers, and to have had prior experience of mental and physical health problems in adult life. Those whose parents had divorced reported more distress in midlife, particularly if they too had experienced marital breakdown. These factors accounted for the associations between some of the adult sources of risk, particularly those to do with interpersonal difficulties or poor adult socioeconomic circumstances, and psychological distress in midlife. There was no evidence that concurrent menopausal status had any effect on the level of psychological symptoms except for those women on hormone replacement therapy who had a small and independent additional risk. More attention to a long term temporal perspective is warranted in research on the causes of psychological distress in women at midlife.