This investigation of 219 hemodialysis patients relates the history and prospective risk of bone fractures to apolipoprotein E (apoE) genotype. A greater percentage of the 41 patients with the E3/4 and E4/4 genotypes than of the 38 patients with the E2/3 and E2/2 genotypes had a history of bone fractures at the time of recruitment (44% versus 16%, P < 0.005). During the 4 years following recruitment, more of the patients with apoE genotypes E3/4 and E4/4 than with apoE genotypes E2/3 and E2/2 suffered bone fractures, but this difference was not statistically significant (17.1 versus 5.3%, P < 0.1). ApoE genotype appears to be an important genetic risk factor for bone fracture, possibly due to its previously reported influence on vitamin K concentrations in blood.