1. The effects of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) and colchicine on acid-base balance were examined in intact and nephrectomized rats.
2. Both drugs increased extracellular hydrogen ion concentrations and depressed extracellular bicarbonate concentrations in nephrectomized rats compared with controls but did not alter these parameters in intact animals.
3. Intracellular hydrogen ion concentrations in the skeletal muscle of nephrectomized rats given EHDP were higher than those of control animals.
4. It is postulated that colchicine and EHDP inhibit skeletal buffering of non-volatile acids produced endogenously in nephrectomized rats.