The microtubular membrane skeleton of Trypanosoma brucei contains two closely related, repetitive, high-molecular-weight microtubule-associated proteins, MARP-1 and MARP-2 (MARP for Microtubule-Associated Repetitive Proteins). Their structure is unusual in that they consist of tandemly arranged, strongly conserved 38-amino-acid repeat units over almost their entire length of about 320 kDa. Their nonrepetitive N and C ends are comparatively short. The predicted amino acid sequences reveal a gradient of similarity between MARP-1 and MARP-2 which increases from the N-terminus (no significant similarity) through the repeat domain (50% similarity) to the C-terminus (94.5% similarity). Transfection of mammalian cell lines with recombinant fragments of MARP-2 demonstrate that the nonrepetitive C-terminus of MARP-2 binds specifically to microtubules. This C-terminus does not show sequence similarity with any other microtubule-associated proteins and thus appears to represent a novel type of microtubule-binding domain.