Dyslipidemia is associated with uremia and an increased risk of cardiovascular disease. The uremic dyslipidemia syndrome is characterized by an abnormal lipoprotein profile that results in (1) an elevation of triglyceride (TG) rich lipoproteins, very low density lipoprotein (VLDL), and intermediate density lipoprotein (IDL); (2) a reduction in high density lipoprotein (HDL) levels; and (3) a higher fraction of atherogenic, small dense low density lipoprotein (LDL). Nocturnal hemodialysis (NHD) is a home based renal replacement therapy that provides better control of uremia than conventional hemodialysis (CHD) and that may improve dyslipidemia. To test this hypothesis, we conducted a prospective cohort study of 11 patients with end-stage renal disease (ESRD) (age 38+/-3 years [mean+/-SEMI) before and after conversion from CHD to NHD. Weight, blood pressure (BP), serum hemoglobin (Hb), phosphate (PO4), and albumin (Alb) were assessed at baseline and at 3 months after conversion to NHD. Dialysis dose on CHD and NHD was assessed using equilibrated Kt/V (eKt/V). A 12 hour fasting lipid profile (total cholesterol [TC], TG, HDL, LDL, HDL/TC) was obtained once while on CHD and at 3 months after conversion to NHD. After conversion from CHD to NHD, eKt/V per session increased significantly (from 1.13+/-0.05 to 2.10+/-0.07; p < 0.05). TG level decreased significantly (from 2.05+/-0.30 to 1.01+/-0.14 mmol/L; p < 0.001), and HDL level increased significantly (from 1.17+/-0.13 to 1.65+/-0.14 mmol/L; p < 0.001). HDL/TC also increased significantly (from 0.26+/-0.03 to 0.35+/-0.02; p < 0.001). TC and LDL levels were unchanged. HDL levels increased and TG levels decreased in all patients. There was no difference in weight, Hb, and Alb. Systolic BP and PO4 were significantly lower, and there was a trend toward a reduction in cardiovascular medications. The mechanism for the improvement in lipid profile requires further study.