Efficient protein folding and quality control are essential for unperturbed cell viability. Defects in these processes may lead to production of aberrant polypeptides that are either degraded leading to "loss-of-function" phenotypes, or deposited in or outside cells leading to "gain-of-toxic-function" phenotypes. Elucidation of molecular mechanisms regulating folding and quality control of newly synthesized polypeptides is therefore of greatest interest. Here we describe protocols for metabolic labelling of transfected/infected mammalian cells with [(35)S]-methionine and [(35)S]-cysteine, for immunoisolation from detergent extracts of the selected model proteins and for the investigation of the model polypeptide's intracellular fate in response to chaperone-deletions or to cell exposure to folding or degradation inhibitors.