Characteristics were identified that predict adaptation following an unsuccessful attempt at in vitro fertilization (IVF). Forty-one women and their husbands were interviewed and administered questionnaires prior to IVF and 2 weeks after notice of a positive or negative pregnancy test. Of the 36 couples who failed to conceive as a result of IVF, 6 of the women studied developed clinical depressive symptoms. Those women who reported poorest adaptation to IVF failure were more likely to have reported depressive symptoms prior to IVF, were more likely to have reported feeling a general loss of control over their lives as a result of infertility, tended to use escape as a coping strategy, and reported having felt some responsibility for their IVF failure. Dispositional optimism, as well as a sense of being partially responsible for the infertility, was protective of distress following IVF failure.