a chimeric toxin comprising protein fragments joined together by peptide bonds , the chimeric toxin comprising , in sequential order , beginning at the amino terminal end of the chimeric toxin , the enzymatically active fragment a of diphtheria toxin , a first fragment including the cleavage domain 1 1 adjacent the fragment a of diphtheria toxin , a second fragment comprising at least a portion of the hydrophobic transmembrane region of fragment b of diphtheria toxin , the second fragment having a deletion of at least 50 diphtheria toxin amino acid residues , the deletion being c - terminal to the portion of the transmembrane region , and the second fragment not including domain 1 2 , and a third fragment comprising a portion of a cell - specific polypeptide ligand , the portion including at least a portion of the binding domain of the polypeptide ligand , the portion of the binding domain being effective to cause the chimeric toxin to bind selectively to a predetermined class of cells to be attacked by the enzymatically active fragment a , the chimeric toxin possessing any of , greater toxicity than that of a toxin comprised of dab 486 fused to the third fragment , a lower k d for the sites on cells of the predetermined class to which the chimeric toxin binds than that of a toxin comprised of dab 486 fused to the third fragment , greater resistance to proteolytic degradation than that exhibited by a toxin comprised of dab 486 fused to the third fragment , greater resistance to the inhibition of its cytotoxicity by the cell - specific polypeptide ligand than that exhibited by dab 486 fused to the third fragment , the ability to inhibit protein synthesis to a given degree by a period of exposure that is shorter than the period of exposure required by dab 489 fused to the third fragment to inhibit protein synthesis to the same degree , or the ability to effect a more rapid onset of the inhibition of protein synthesis than that exhibited by dab 486 fused to the third fragment .