The association between insulin resistance (IR) and depression is a subject of growing research interest, especially as previous population-based studies have presented conflicting findings. The present study extends our understanding about the putative impact of the severity of depressive symptoms on this association and it provides further epidemiological evidence in support of earlier findings, suggesting that the association between IR and depression is present already in young adult males. To determine the impact of the severity of depressive symptoms on the putative association between IR and depression in young adult males, we were given access to the Northern Finland 1966 Birth Cohort database. During the 31-year follow-up survey of this genetically homogeneous birth cohort, IR was assessed by 'Qualitative Insulin Sensitivity Check Index' (QUICKI), and severity of depressive symptoms by 'Hopkins' Symptom Checklist-25' (HSCL-25). This study involved 2609 male cohort members with complete variable information. In men, the means of the QUICKI-values decreased (i.e., IR increased) in line with the increased severity of depressive symptoms as assessed by HSCL-25 subgroups (analysis of covariance P-value for trend, P=0.003). In multivariate generalized logistic regression analyses, after adjusting for confounders, IR was positively associated with current severe depressive symptoms, the odds ratio (OR) being over threefold (adjusted OR 3.15, 95% confidence interval 1.48-6.68) and the value of OR increased in parallel with a tighter definition of IR (P-value for trend=0.007). The results indicate that in young males, a positive association exists specifically with severe depressive symptoms.Molecular Psychiatry advance online publication, 9 May 2006; doi:10.1038/sj.mp.4001838.