Despite advances in the delivery of hemodialysis, significant dialytic morbidity persists. Sodium modeling in older adults has been shown to decrease some dialytic symptoms, but clear benefits in young patients without coexisting diabetes or advanced cardiovascular disease have not been shown. The effects of sodium modeling were evaluated in 16 adolescent and young adult hemodialysis patients (16 to 32 yr of age) treated with conventional hemodialysis for a median of 11.5 months. The 8-wk study was divided into four 2-wk blocks. During each block, one of three sodium programs or a constant (control) dialysate sodium of 138 mEq/L was used. During each sodium program, the initial dialysate sodium of 148 mEq/L was decreased by an exponential, linear, or step program to 138 mEq/L. Treatments with sodium modeling were significantly better than those with constant sodium dialysate. When all sodium programs were grouped and compared with constant dialysate sodium, the odds of improvement in dialytic cramps, headaches, and nausea were 1.8, 2.1, and 3.9, respectively (P < 0.05). Sodium modeling also significantly decreased the frequency of postdialysis hypotension and interdialytic fatigue, dizziness, and muscle cramping (P < 0.05). No differences were seen among the sodium protocols in the incidence of symptomatic hypotension, the amount of normal saline administered, the degree of hemo-concentration during treatments, or the decrease in serum osmolality. There was no increase in pretreatment or posttreatment serum sodium concentrations, interdialytic thirst, weight gain, or hypertension. Sodium modeling dramatically decreases both intradialytic and interdialytic morbidity in young hemodialysis patients. There was no increase in adverse events associated with sodium modeling.