The effect of triethyltin-chloride (TET), a highly neurotoxic compound, on the cellular metabolism of rat brain astrocytes in vitro was examined by nuclear magnetic resonance (NMR) spectroscopy. 5-week-old cultures were exposed to TET (0.2-40 microM) either for (1) acute (3h), (2) 24 h, or (3) chronic treatment (8 d). Cells were labeled with 1-(13)C-glucose, cell extracts were prepared and 31P, 1H, and 13C spectra were analyzed. Cytotoxic effects of TET were assessed by vital dye uptake assay using neutral red (NR) and by exclusion of trypan blue (TB). Cells were examined ultrastructurally by electron microscopy. The data show that the major target of TET at concentrations already causing morphological effects on cultured astrocytes is not the energy metabolism, but that TET rather alters the intracellular concentrations of organic osmolytes, such as myo-inositol, taurine and hypotaurine, which are part of the control of ion and volume regulation and osmotic balance in astrocytes.