End-stage renal disease affects every aspect of a patient's life, including perception of health and quality of life. It is likely that a hemodialysis patient's perceptions of health-related quality of life directly influence compliance with medical, nursing, and nutritional prescriptions. Because L-carnitine supplementation is known to enhance muscle strength and energy in hemodialysis patients, we hypothesized that L-carnitine supplementation would enhance a hemodialysis patient's perception of health-related quality of life. To test this hypothesis, 1 g L-carnitine or placebo was administered orally to 101 patients immediately before and after every hemodialysis treatment for 6 months. To assess health-related quality of life from the patient's perspective, the Medical Outcomes Study Short Form 36 instrument was administered before the study and at 1.5-month intervals for the duration of the study. In addition, a 10-item questionnaire designed to assess common intradialytic symptoms was administered at the end of each dialysis treatment. Other parameters analyzed included Kt/V(urea) and level of nutrition. In the 6-month group, oral L-carnitine supplementation had an early positive effect on general health (P < 0.02) and physical function (P < 0.03), but the perceived effect was not sustained throughout the 6 months of the study. In the 3-month group, L-carnitine supplementation improved vitality (P < 0.02) and general health (P < 0.01). There was no association between Kt/V(urea) and perceived health-related quality of life. Serum albumin concentration was directly correlated to how patients perceived the quality of their lives.