An in vitro model system has been developed to establish dose-response relationships of mercuric chloride (HgCl2) and methylmercuric chloride (HgCH3Cl). Mouse neuroblastoma cell cultures (Neuro-2a) were exposed for 24 hr and cytotoxic effects evaluated with eight different endpoints. Toxic indicators assessed in the in vitro test system were as follows: cell proliferation by quantification of total protein content; cytoplasmic membrane integrity by cytosolic lactate dehydrogenase leakage; lysosomal membrane stability by hexosaminidase release; lactate dehydrogenase activity; mitochondrial succinate dehydrogenase activity; relative neutral red uptake by lysosomes; lysosomal hexosaminidase sphingolipid degradation activity; acetylcholinesterase activity. The toxicity of the two chemical species of mercury on neuroblastoma cells differed. HgCl2 inhibited LDH activity specifically and very potently. Gross disruption of cytoplasmic membrane was accompanied by stimulation of hexosaminidase. HgCH3Cl was 50 times more toxic than HgCl2 to Cell proliferation and also caused important alterations in both membrane stability and metabolic activities over a narrow range of doses. The data suggest that HgCl2 acts mainly on cell membranes and LDH, whereas, although HgCH3Cl is more cytotoxic, it does not affect any of the above-mentioned endpoints as specifically.