Objective: To assess the incidence of depression, and the ability to interact socially, in adult patients with chronic cyanosis and congenital cardiac malformations. Design: Prospective study of consecutive patients. Setting: Single institution, tertiary referral centre. Patients: Between 1993 and 2000, we assessed 76 patients with congenital cardiac malformations and persistent cyanosis, having a median age of 36.5 years, with a range from 19 to 64 years, at the time of referral. Female patients accounted for just under half (48.6%) of the sample. Just under two-fifths of the cohort (39.5%) had functionally univentricular cardiac anatomy, while 14.8% had tetralogy of Fallot with pulmonary atresia and aorto-pulmonary collateral arteries, and 17% had the Eisenmenger syndrome. During the period of follow-up, 17 (22.4%) of the patients died. Assessment: We used clinical interviews and non-invasive assessment, employing Zung's questionnaire which provides a scale for the self-rating of depression. On this scale, a score above 50 points is indicative of depression. Results: Of the survivors, 32 (54%) completed the self-rating questionnaires. Of these, 20 responders (63%) considered that they lead full lives, including sexual activities, while 26 (81%) had never harboured suicidal thoughts. Depression was diagnosed in 11 responders (34%), with a mean score of 66.9, standard deviation of 8.7, and a range from 53 to 89. The remaining 21 patients (66%) were without signs of depression, scoring a mean of 41.5, with standard deviation of 5.5, and a range from 35 to 46. Depression was associated with older age (40.5 years versus 33.5 years, p =0.01), worse functional state in the classification of the New York Heart Association (2.95 versus 2.48, p =0.03), and unemployment (p < 0.0001), but independent from the severity of cyanosis, the level of the haematocrit, the saturation of oxygen, or previous surgical treatment. Conclusions: To our knowledge, this is the first evidence suggesting a relatively high incidence of depression in adults with congenital cardiac malformations and persistent cyanosis. Larger, multi-centric studies will be needed to confirm or refute these findings.