Chrysotile asbestos is cytotoxic for rabbit polymorphonuclear leukocytes (PMNs) which is evident from the release of the cytoplasmic enzyme LDH. In the presence of Ca2+, but not in its absence, a strong lysozyme release occurs. High concentrations of Ca2+ are required for exocytosis. In the presence of the stable guanine nucleotide GTP gamma S exocytosis occurs at lower Ca2+ concentrations. The results suggest that the plasma membrane is permeabilized by asbestos, allowing the influx of extracellular Ca2+ which causes exocytosis. At high Ca2+ concentrations asbestos-induced cytotoxicity is strongly reduced. The cytotoxic LDH release and, to a lesser degree, the exocytotic enzyme release are inhibited by Co2+, Mn2+ and La3+. Cytochalasin B and the glycolytic inhibitors 2-deoxyglucose and iodoacetate inhibit asbestos-induced cytotoxicity, indicating that microfilaments and glycolytic energy are required for the membrane-damaging actions of asbestos.