Chinese hamster ovary cells were used to examine the effect of emetine upon the toxicity of T-2 toxin and several related trichothecene inhibitors of polypeptide synthesis. Emetine inhibited protein synthesis and T-2 toxin-cell association in a concentration-dependent manner. The dose-response curves for these two effects were nearly identical. Over a narrow concentration range (0.3-3.0 micrograms/ml), emetine's inhibition of protein synthesis was partially reversible, whereas its inhibition of toxin-cell association was maintained for extended periods. This sustained inhibition of toxin-cell association, resulted in "desensitized" cells with reduced sensitivity to the inhibitory effects of T-2 toxin on protein synthesis. Similar results were obtained when emetine-preincubated cells were challenged with diacetoxyscirpenol, verrucarin A and roridin A. In contrast, there were no measurable effects of emetine upon the response of the cells to the less potent trichothecenes, deoxynivalenol, T-2 tetraol and verrucarol. In addition to emetine, several other inhibitors of polypeptide synthesis were examined for their effects on T-2 toxin-cell association and sensitivity to T-2 toxin. Of these, only cycloheximide inhibited toxin-cell association. Unlike emetine, sustained protection against the effects of T-2 toxin was not observed with cycloheximide.