Regulation of pHi in the face of acidosis resulting from contracture would appear to be of such fundamental importance to the physiology of the muscle cell that a process common to all muscle types seems a reasonable prediction. However, this has not been found to be the case. The transmembrane Na+ gradient clearly plays a major role and the process appears to be electroneutral in all three classes of muscle, but the transport mechanisms, even within the mammal, are different. It is an interesting observation that the ability of the muscle cell to regulate pHi in the presence of CO2, presumably governed by PHCO3, is related to PCl although there is little evidence for HCO3- permeation through Cl- channels. Virtually no recovery from CO2-induced acidosis is observed in normally polarized frog skeletal muscle, where PCl forms a large part of the resting conductance, whereas the same steady state pHi is recorded in the presence of various CO2 levels in mammalian smooth muscle, where PCl is very low. The study of pHi regulation in vertebrate muscle has provided important lessons for the subject as a whole. Experience in cardiac muscle has shown that if Na+-Ca2+ exchange is present, great care is required in interpretation of results where the transmembrane Na+ gradient is altered or where Ca2+ levels are changed. Interpretation may be even more complex, bearing in mind the recent reports that Ca2+ inhibits Na+-H+ exchange. "Indeed," it seems appropriate to conclude, "if a little knowledge is dangerous, where is the man who has so much as to be out of danger?" (Thomas Huxley).