Cells of Mycoplasma gallisepticum incubated in 250 mM NaCl in the absence of glucose for several hours show swelling and eventual lysis. This swelling is believed to be due to colloid osmotic and Donnan forces, since it is prevented by the addition of nondiffusable solutes such as sucrose or MgSO4. The addition of glucose during the swelling stage (but before lysis) caused shrinkage and return to initial volume. Experiments on Na+ and H+ movement are consistent with the operation of an ATP-driven H+ pump and a Na+/H+ exchange reaction.