The constancy of cell volume under physiological conditions is general
ly thought to reflect a balance between solute influx and efflux and i
s therefore critically dependent on the properties of the plasma membr
ane. Despite a number of unanswered questions, a large amount of exper
imental data can be accommodated within this pump-leak framework and c
an by analysed using the simple assumptions of osmotic equality betwee
n cells and their surrounding fluid, and fluid electroneutrality. Expe
rimentally, cell volume may be altered in vitro either by changing cel
l solute content under isosmotic conditions or by changing medium osmo
lality. Exposure to anisosmotic media may provoke a variety of cell re
sponses that minimise the volume change. However, much of this experim
ental work has been performed under extreme conditions in vitro that w
ould never be experienced by vertebrate cells in vivo; its relevance t
o pathophysiological situations is questionable. It is argued that reg
ulation of cell volume should not be seen in isolation but as part of
the process, cell homeostasis, by which cells attempt to minimise chan
ges in composition when faced with perturbations in their environment.
Given the variety of processes and the large numbers of membrane tran
sporters, an understanding of how cells respond to such perturbations
requires a combination of modelling and experimentation. A simple exam
ple of this approach is presented. (C) 1994 Wiley-Liss,Inc.