In a double-blind, crossover trial, 7 chronic hemodialysis patients underwent three 4-week treatment periods. During one period, dialysate contained 135mEq/l sodium. During another period, dialysate contained 143 mEq/l sodium. During the remaining period, we used ‘sodium gradient’ dialysate, the sodium concentration of which was decreased from 160 to 133 mEq/l during each 4-hour dialysis session. Ultrafiltration was performed at a constant rate to achieve a predetermined post-dialysis weight. Interdialytic weight gain, thirst, blood pressure control, and incidence of side effects were monitored. There was a significant difference in interdialytic weight gain for the 3 treatments (p = 0.005). Interdialytic weight gain using 135mEq/l sodium dialysate (2.2 ± 0.9 kg, mean ± SD) was significantly less than that using either 143 mEq/l sodium dialysate (2.6 ± 0.8 kg) or sodium gradient dialysate (2.8 ± 0.7 kg). Self-reported thirst tended to be less severe with 135 mEq/l sodium dialysate than with 143 mEq/l sodium dialysate or with sodium gradient dialysate, but changes in thirst were not statistically significant (p = 0.13). The incidence of intradialytic hypotensive episodes was comparable with the 3 levels of dialysate sodium. The results suggest that the described sodium gradient method does not prevent the increased interdialytic weight gain and thirst seen with other forms of high-sodium dialysis, and probably does not reduce the incidence of side effects.