Renal handling of salt and water during water diuresis was studied in the same 7 healthy subjects before and after the administration of tolinase. After tolinase there was no change in mean values of Cinulin, Cp-aminohipurate and calculated rate of distal sodium delivery (CH2O + CNa/100 ml glomerular filtration rate). Mean filtration fraction fell from 19.3 ± SD3.5to 16.8 ± 3.3% (p < 0.01). The mean fraction of delivered sodium reabsorbed at the diluting site (CH2O/[CH2O + CNa]) rose from 83.3 ± SD 3.6 to 88.0 ± 3.3% (p < 0.05). Mean minimal urinary osmolality fell from 85.9 ± SD 8.6 to 69.4 ± 10.3 mOsm/kg H2O (p < 0.01). Free water clearance for a given rate of urine flow was higher following tolinase than in controls. Mean rate of urinary potassium excretion fell following tolinase (p < 0.05). Maximal urinary concentration following 24 h fluid deprivation was unchanged by tolinase either in man or in the dog. Augmented tubular reabsorption of sodium at the diluting site appears to underly the lowering of minimal urinary osmolality following tol