Damage to the central nervous system (CNS) is selective, likely reflecting the intrinsic properties of -individual cell types. Targets of chemical injury are diverse hence assessing neurotoxicity is extremely difficult. Overcoming this obstacle requires a general screen or "marker" for injury that reflects cellular damage. The "marker" must be reliable and represent a biochemical event which broadly reflects cellular stress and damage. One such "marker" is cell swelling; it occurs in response to a diversity of insults, such as physical damage, disease (ischemia, trauma, and hypoxia), and chemicals (methylmercury, lead, 1,3-dinitrobenzene, and triethyltin). In astrocytes, a type of glia, astrocytic swelling can be measured with several methods. Commonly, freshly isolated astrocytes are grown to confluence on coverslips, a period requiring 3 weeks in culture. At this time, astrocytic volume can be measured using either an impedance technique or 3-O-methyl-D-glucose to assess cell volume. This review will briefly detail these methods and provide insight into molecular mechanisms associated with cell swelling and the ensuing regulatory decrease (RVD).