The effects of T-2 toxin on protein synthesis, respiratory chain activity of the mitochondria, cell lysis and toxin-cell binding were compared in the toxin-sensitive bovine kidney cell line (MDBK) and in the toxin-resistant Chinese hamster ovary cell line (CHO). Protein synthesis and mitochondrial activity were 10-fold less sensitive in CHO cells as compared to MDBK (50% inhibition=10–15 ng/ml vs. 1–1.5 ng/ml, respectively). Lytic activity, as determined by release of 51Cr from cells incubated at 4°C, was not detected at 5h or 24h in either of the cell lines. However, at 24h, CHO cells released less 51Cr than non-toxin-exposed controls, indicating that some membrane interaction does occur. Both cell lines equally bound [ 3H]T-2 toxin at 4°C. At 37°C, the MDBK cells take up twice as much [ 3H]T-2 toxin at 2h and 6h. These results indicate that T-2 toxin mediates a number of effects on the cell at the level of the membrane, protein synthesis and probably mitochondrial activity toward 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction.