When exposed to neuroleptics (100 microM), C6 glioma cells exhibited marked changes in cell morphology, accompanied by cessation of cell division and ultimately cell death. The degree of activity generally correlated with binding affinity at sigma sites: fluphenazine = perphenazine = haloperidol = reduced haloperidol > pimozide = spiperone >> >> (-)-sulpiride. Sigma-inactive compounds (100 microM) which block dopamine, serotonin, phencyclidine, muscarinic receptors and adrenoceptors showed no effect. These results may suggest a role of sigma binding sites in maintenance of cell viability.