Lipid synthesis from 14C-labeled acetate was dramatically reduced by inorganic mercury in the mouse sciatic nerve in vitro (IC50 was 10 microM). The dysmyelinating trembler mutant was less affected (IC50 was 40 microM). Under the same conditions, lipid synthesis was less inhibited by inorganic lead but was increased 3 times by manganese, copper and nickel at less than 2 mM. Although the synthesis of all lipids is dramatically reduced by inorganic mercury, their relative proportions vary in the presence of this metal:cholesterol synthesis was inhibited most strongly, phosphatidylcholine synthesis was also reduced, whereas synthesis of other lipids was relatively unchanged (phosphatidylserine, phosphatidyl inositol, sphingomyelin, cholesterol esters, cerebrosides). Incorporation of [14C]acetate into free fatty acids was enhanced by a factor of 4 in the presence of inorganic mercury.