Flow cytometric studies of mouse thymocytes show that technical toxaphene (10-20 ppm) and 2,5-dichloro-3-biphenylol (PCB 9-OH) (5-10 ppm) kill cells and cause an increase in intracellular calcium concentration, [Ca2+]i, whereas commercial octabromodiphenylether (OBDE) has no effect. The cell death is not a result of the rise of [Ca2+]i, since the divalent cation ionophore, ionomycin, causes a large elevation in [Ca2+]i without cell death. We have studied effects of these compounds on membrane fluorescence polarization, a measure of membrane fluidity, using 1,6-diphenyl-1,3,5-hexatriene (DPH). We find that toxaphene causes a decrease in membrane fluidity in the concentration range associated with cell death, whereas PCB 9-OH causes an increase in fluidity and OBDE has no effect. These observations suggest that alterations of membrane fluidity of thymocytes, whether it be an increase or decrease, can cause cytotoxicity.