BACKGROUND Norplant is a relatively new long-acting subdermal implant system that is used widely for contraception. In a recent report, Wagner and Berenson described two cases of Norplant-associated major depression and panic disorder. These were the first reports of severe psychiatric disorders linked to the use of Norplant. METHODS Five cases are described of women who developed major depression, two of whom also developed obsessive-compulsive disorder and one of whom also developed agoraphobia, while using the Norplant system. RESULTS These women who had no prior psychiatric history developed major depression within 1 to 3 months after Norplant insertion. The depression worsened over time and in all cases resolved within 1 to 2 months after Norplant removal. There was no recurrence of depression after 7 to 8 months in four cases available for follow-up. In addition to major depression, obsessive-compulsive disorder developed in two women and symptoms of agoraphobia developed in one woman during Norplant treatment, which resolved after Norplant removal. CONCLUSIONS These cases provide further support for the association between Norplant and major depression, as well as a broad spectrum of anxiety disorders. It is important to design prospective studies to carefully examine the incidence of major depression and anxiety disorders in women who use Norplant. Risk factors for these disorders require further clarification.