High-resolution two-dimensional (2D) (1)H-(15)N heteronuclear correlation (HETCOR) spectroscopy has been used to characterize the structure and dynamics of (15)N-backbone labeled antimicrobial piscidin 1 (p1) oriented in "native-like" hydrated lipid bilayers. Piscidin belongs to a family of amphipatic cationic antimicrobial peptides, which are membrane-active and have broad spectrum antimicrobial activity on bacteria. When the (1)H chemical shifts are encoded by the (1)H-(15)N dipolar couplings, 2D dipolar-encoded HETCOR (i.e., de-HETCOR) solid-state NMR spectra yield high resolution (1)H and (15)N chemical shifts as well as (1)H-(15)N heteronuclear dipolar couplings. Several advantages of HETCOR and de-HETCOR techniques that emerge from our investigations could facilitate the atomic-level investigations of structure-function relationships in membrane-active peptides and membrane-bound species. First, the de-HETCOR NMR spectrum of a ten-site (15)N-labeled sample of p1 aligned in hydrated lipid bilayers can resolve resonances that are overlapped in the standard HETCOR spectrum. Second, the resolution in de-HETCOR spectra of p1 improves significantly at higher magnetic field due to an enhanced alignment that improves spectrum definition uniformly. Third, the HETCOR spectrum of (15)N-K(14) p1 oriented in hydrated lipid bilayers displays not only the expected crosscorrelation between the chemical shifts of bonded amide(1)H and (15)N spins but also a cross peak between the (1)H chemical shift from bulk water and the (15)N chemical shift from the labeled amide nitrogen. This information provides new insights into the intermolecular interactions of an amphipathic antimicrobial peptide optimized to partition at the water-bilayer interface and may have implications at the biological level.