Major depression is a multifactorial disorder. Previous studies have mainly evaluated work stress to determine the risk factors for depression among workers. The present study aimed to determine factors predictive of the first depressive episode 1 year later among white-collar workers, and to examine whether work 'stress' is associated with an elevated risk of depression. A 5 year open-cohort study was carried out in a Japanese company. The odds ratios (OR) of the development of depression 1 year later were calculated. Ninety-eight first-onset cases were compared with 1267 never-ill cases. Forward stepwise multiple logistic regression indicated that the first onset of depression was associated with a past history of panic attack (OR: 5.14; 95% confidence interval (CI): 1.64-16.10), neuroticism (OR: 3.59; 95%CI: 2.06-6.26), perceived overprotection (OR: 2.75; 95%CI: 1.66-4.55), poor support (OR: 2.55; 95%CI: 1.58-4.10), and low care (OR: 2.23; 95%CI: 1.23-4.04). First-onset cases were more likely to have had objective work events (OR: 1.50; 95%CI: 1.18-1.90) but they did not differ from never-ill cases in subjective job stress. The development of major depression in white-collar workers is associated with multiple factors, as is depression in the community.