Vulnerability at long-term unemployment is discussed and the results of a study of the effects of job loss and long-term unemployment among Swedish women are presented. Psychological and physiological data for the unemployed were sampled repeatedly over a two year period. Some of the unemployed were subject to an intervention programme aiming at buffering for the possibly negative effects of unemployment. Health data from matched control groups of employed were gathered over the same period. The results indicate a strong negative stress reaction at the job loss period, followed by a gradual adaptation to the conditions of unemployment as measured by biochemical and physiological health indicators. However, a substantial proportion of the unemployed compared to the employed showed a lower degree of psychological well-being and more severe depressive reactions. Recommendations are given concerning further research approaches on long-term unemployment. Policy implications to reduce vulnerability at long-term unemployment are discussed.