BACKGROUND: The role of allelic variation in APOE, the genetic locus for apolipoprotein E, in geriatric depression is poorly understood. There are conflicting reports as to an association between the epsilon4 allele and depression in late life. METHOD: Using a community based study of non-demented elders in Cache County, Utah, that included many very old individuals, we examined the relationship between APOE and late-onset (age > 60) depression, with particular attention to possible age effects. RESULTS: There was no overall association between APOE and depression. However, there was a significant interaction effect of APOE and age such that the relationship of late-onset depression with respect to presence of the epsilon4 allele was larger among those 80 and older compared with those below age 80. Consistent with previous studies, women were more likely to experience late-onset depression than men. CONCLUSIONS: Because we excluded prevalent cases of dementia, this pattern of relative risk with age may reflect the appearance of depressive symptoms as a prodrome of Alzheimer's disease or vascular dementia. Longitudinal studies should help to confirm or refute this explanation of the data.