Telomere length shortens with cellular division, and leukocyte telomere length is used as a marker for systemic telomere length. The hippocampus hosts adult neurogenesis and is an important structure for episodic memory, and carriers of the apolipoprotein E epsilon4 allele exhibit higher hippocampal atrophy rates and differing telomere dynamics compared with non-carriers. The authors investigated whether leukocyte telomere length was associated with hippocampal volume in 57 cognitively intact subjects (29 epsilon3/epsilon3 carriers; 28 epsilon4 carriers) aged 49-79 yr. Leukocyte telomere length correlated inversely with left (r.sub.s = -0.465; p = 0.011), right (r.sub.s = -0.414; p = 0.025), and total hippocampus volume (r.sub.s = -0.519; p = 0.004) among APOE epsilon3/epsilon3 carriers, but not among epsilon4 carriers. However, the epsilon4 carriers fit with the general correlation pattern exhibited by the epsilon3/epsilon3 carriers, as epsilon4 carriers on average had longer telomeres and smaller hippocampi compared with epsilon3/epsilon3 carriers. The relationship observed can be interpreted as long telomeres representing a history of relatively low cellular proliferation, reflected in smaller hippocampal volumes. The results support the potential of leukocyte telomere length being used as a biomarker for tapping functional and structural processes of the aging brain.