Depressive disorders are a leading cause of disability in older age. Although the role of psychosocial and behavioural predictors has been well examined, little is known about the biological origins of depression. Findings from animal studies have implicated insulin-like growth factor 1 (IGF-1) in the aetiology of this disorder. A total of 6017 older adults (mean age of 65.7 years; 55% women) from the English Longitudinal Study of Ageing provided serum levels of IGF-1 (mean=15.9 nmol l(-1), s.d. 5.7) during a nurse visit in 2008. Depression symptoms were assessed in the same year and again in 2012 using the eight-item Center for Epidemiologic Studies Depression Scale. Self-reports of a physician-diagnosis of depression were also collected at both time points. In separate analyses for men and women, the results from both the cross-sectional and longitudinal analyses revealed a 'U'-shaped pattern of association, such that lower and higher levels of IGF-1 were associated with a slightly elevated risk of depression, whereas the lowest risk was seen around the median levels. Thus, in men, with the lowest quintile of IGF-1 as the referent, the age-adjusted odds ratios (95% confidence interval) of developing depression symptoms after 4 years of follow-up, for increasing quintiles of IGF-1, were: 0.51 (0.28-0.91), 0.50 (0.27-0.92), 0.63 (0.35-1.15) and 0.63 (0.35-1.13) (P-value for quadratic association 0.002). Some attenuation of these effects was apparent after adjustment for co-morbidity, socioeconomic status and health behaviours. In conclusion, in the present study of older adults, there was some evidence that moderate levels of IGF-1 levels conferred a reduced risk of depression.