Hepatitis B virus (HBV) vaccination is recommended for all individuals with renal failure. Nevertheless, the response rate for this vaccine in hemodialysis (HD) patients is low, ranging from 50% to 80%. The goal of this study was to determine patient characteristics at the initiation of HD that influence HBV vaccine response. Patients new to HD in an urban population in the United States were retrospectively examined. Analyzed patients were HBV antibody and antigen negative and hepatitis C virus antibody negative at the start of HD, who received HBV recombinant vaccine. Nonresponse was defined as failure to seroconvert (>10 UI/L) after six deltoid intramuscular injections of vaccine. Response was defined as a lasting seroconversion (at least two consecutive positive titers) with </=6 injections. Demographic, laboratory, and kinetic modeling data were examined. A total of 33 nonresponders and 64 responders were identified. Univariate analysis demonstrated that nonresponders were older (59 vs. 51 years), had a higher prevalence of diabetes mellitus (DM) (70 vs. 39%), had lower serum albumin levels (3.2 vs. 3.3 g/dL), and had higher dry weights (84 vs. 71 kg) than responders at HD start. In addition, nonresponders had lower normalized protein catabolic rates (0.74 vs. 0.85 g/kg/day) and lower (single-pool) spKt/V(urea)values (0.95 vs. 1.19). Nonresponders had lower serum creatinine levels than responders, despite the greater dry weights. In a multiple logistic analysis model, the presence of DM, age >/= 55 years, body weight >/=80 kg, and normalized protein catabolic rate </=0.75 g/kg/day were associated with HBV vaccination nonresponse. At the end of the vaccination period, nonresponders versus responders continued to have lower serum albumin (3.5 vs. 3.8 g/dL) and creatinine levels (7.8 vs. 10.0 mg/dL) and spKt/V(urea)(1.27 vs. 1.39). Hepatitis B vaccine nonresponders on HD are older, are more likely to have DM, are more malnourished, and have lower spKt/V(urea) than responders. Nonresponders may also have a different body composition with a lower ratio of lean to total body mass.