The N-terminal 22 residues of the envelope glycoprotein 41,000 (gp41) of HIV have been implicated in the process of viral fusion with the target cell membrane. This gp41 fusion peptide (FP) has a highly conserved hydrophobic sequence, containing a tandem repeat of the tripeptide Phe-Leu-Gly, with extensive homology to the fusion peptides of other paramyxoviruses. FTIR and CD studies and theoretical calculations suggest that the gp41 FP inserts into the phospholipid membrane at an oblique angle, with residues 519 to 533 in an a-helical conformation, and the remaining peptide in a random conformation. Solid-state NMR studies of the selectively 15N labeled gp41 FP were conducted to ascertain the veracity of this model. The petide was incorporated into lipid bilayers and oriented on glass plates. The 15N chemical shift spectrum of gp41 FP labeled in position Ala-524 indicates that the amide bond is oriented with the helix axis paralell to the bilayer normal. The 15N spectra from Ala-253 and Gly-254 reflect a mixture of random and transmembrane conformations, as might be expected for a conformational transition zone. Ala-539 gives an 15N spectrum characteristic of random conformation.