Thiazide diuretics increase salt and water excretion primarily by inhibiting mechanisms for electroneutral sodium and chloride transport by distal convoluted tubule cells. This might be termed the ‘specific’ effect of this class of diuretics and accounts for the ‘chlorouretic’ effectiveness of the drug. Secondary to this inhibition of sodium and chloride absorption, potassium secretion is stimulated most likely because of the resultant increase in distal tubule fluid flow rate, and calcium absorption is stimulated possibly via a decrease in distal convoluted tubule cell sodium activity and an increase in basolateral sodium/calcium exchange. To a varying degree, thiazides also inhibit carbonic anhydrase. This effect can contribute to the diuresis, but is largely buffered by the reserve transport capacity of the loop of Henle. To the extent that the effects of transport inhibition in the proximal tubule are transmitted to the distal tubule, tubuloglomerular feedback may be activated and effect a reduction in the glomerular filtration rate.