This study evaluated whether lead acetate or other selected metal salts would influence the binding of L-tryptophan to rat hepatic nuclei. Lead salts and other salts of cadmium, zinc, mercury, and molybdenum, when added alone, had only small effects on 3H-tryptophan binding to hepatic nuclei in vitro. However, each of these salts, when added along with unlabeled L-tryptophan (excess, 10(-4) M), caused significantly less inhibition of 3H-tryptophan binding to hepatic nuclei than did unlabeled L-tryptophan alone. Lead acetate (10(-10) to 10(-4) M), when added along with unlabeled L-tryptophan, abrogated the inhibition of binding related to unlabeled L-tryptophan alone. Sodium arsenite (but not potassium arsenate) as well as sodium selenite (at 10(-4) M concentrations) inhibited to a moderate degree the in vitro 3H-tryptophan binding to hepatic nuclei, but addition of 10(-4) dithiothreitol, a protective agent for sulfhydryl groups, diminished this inhibition. Rats receiving a high dose of lead acetate before being tube-fed L-tryptophan displayed a decrease in hepatic protein synthesis compared with the stimulatory response connected with L-tryptophan alone. Thus, the addition of lead acetate and of other metal salts appears to have an inhibitory effect on L-tryptophan binding to hepatic nuclei. Lead acetate was investigated in in vivo experiments and was found to negate the stimulation of hepatic protein synthesis related to L-tryptophan alone.