Perturbation of brain protein synthesis by methyl mercury chloride (MeHg) was compared in vivo and in vitro. MeHg-stimulated and/or inhibited brain cell-free protein synthesis following in vivo or in vitro administration. Although pretreatment with GSH protected the postmitochondrial supernatant (PMS) from the in vitro inhibition, direct addition of -SH compounds did not reverse the in vivo or in vitro perturbations in synthesis induced by MeHg. Inhibition of synthesis induced by both in vivo and in vitro methyl mercury administration resulted in inactivation of component(s) in brain pH 5 enzymes. Stimulation of amino acid incorporation following in vivo administration of MeHg was apparently associated with the ribosome fraction, but in vitro preincubation of PMS with MeHg produced stimulation associated with the pH 5 enzyme fraction. A model of MeHg neurotoxicity was proposed providing a common molecular locus of interaction in vivo and in vitro.