The amino acids in the heme pocket of sperm whale myoglobin single E11 and double E7 and E11 point mutants in the metcyano form have been assigned by NMR methods to assess the role of steric bulk in modulating ligand tilt. The five mutants investigated are the single mutants His64(E7)-->Gly (H[E7]G), Val68(E11)-->Ile (V[E11]I), and Val68(E11)-->Ala (V[E11]A) and the double mutants His64-(E7)-->Gly:Val68(E11)-->Ile (H,V[E7,E11]G,I) and His64(E7)-->Gly:Val68(E11)-->Ala (H,V[E7,E11]G,A). The dipolar (NOESY) contacts on the proximal side of the heme confirm a conserved molecular structure for all of the mutants. The proximal residue coordinates, together with the dipolar shifts for proximal side residues, quantitatively yield the orientations of the magnetic susceptibility tensors, whose major axis corresponds to the orientation of the ligand. It is observed that upon reduction of the steric bulk in the V[E11]A mutant, the tilt of the ligand is significantly reduced (approximately 8 degrees) from that in the wild type (WT) (approximately 16 degrees), with little change in the direction of tilt. In the case of increased steric bulk at position 68 in the V[E11]I mutant, it is observed that the extent and direction of the tilt are essentially the same as in WT, and it is shown that this is due to the fact that Ile68 is oriented in the pocket with its C delta H3 directed away from the iron.(ABSTRACT TRUNCATED AT 250 WORDS)