The integral membrane protein M2 of influenza A virus assembles as a tetrameric bundle to form a proton-conducting channel that is activated by low pH. The side chain of His(37) in the transmembrane a-helix is known to play an important role in the pH activation of the proton channel. It has also been suggested that Trp(41), which is located in an adjacent turn of the helix, forms part of the gating mechanism. Here, a synthetic 25-residue peptide containing the M2 transmembrane domain was labeled with 6F-Trp(41) and studied in lipid membranes by solid-state F-19 NMR. We monitored the pH-dependent differences in the F-19 dipolar couplings and motionally narrowed chemical shift anisotropies of this 6F-Trp(41) residue, and we discuss the pH activation mechanism of the H+ channel. At pH 8.0, the structural parameters implicate an inactivated state, while at pH 5.3 the tryptophan conformation represents the activated state. With the aid of COSMOS force field simulations, we have obtained new side-chain torsion angles for Trp(41) in the inactivated state (chi(1) = -100 degrees +/-10 degrees, chi(2) +110 degrees +/- 10 degrees), and we predict a most probable activated state with chi(1) = -50 degrees +/- 10 degrees and chi(2) +115 degrees +/- 10 degrees. We have also validated the torsion angles of His(37) in the inactivated state as chi(1) = -175 degrees +/-10 degrees and chi(2) = -170 degrees +/- 10 degrees.