Abstract The administration of a diet containing 7.5% saccharin ad libitum to adult male rats for 1 month increased the daily excretion of indican. The maximum urinary excretion of saccharin which occurred during the night (2000-0800h), was associated with a reduced renal elimination of indican. This resulted in proportionately greater renal excretion of indican during the day, which has been shown previously to be the time of maximum distension of the urinary bladder in rats fed a saccharin containing diet. Thus the physiological and biochemical changes produced by high dietary levels of saccharin, i.e. saturation of renal tubular secretion, increased excretion of indican and bladder distension are inter-related such as to maximise the possible interaction of the bladder epithelium with endogenous substrates of renal tubular secretion.