Intermolecular H-1{F-19} NOE experiments have been used to explore the interactions of trifluoroethanol (TFE) with the octapeptide hormone [val(5)]angiotensin II at temperatures from 5 to 25 degrees C. Circular dichroism spectra indicate that 40% trifluoroethanol has an influence on the conformations of the peptide, probably leading to beta-structures. Diffusion experiments show that the mean hydrodynamic radius of the peptide in 40% trifluoroethanol-water is about 8 A, consistent with significant folding of the peptide in this medium. Distance constraints derived from intramolecular NOESY data along with observed vicinal coupling constants ((3)J(C alpha HNH)) were used to develop conformations consistent with available data. Assuming that intermolecular H-1{F-19} NOEs are the result of diffusive encounters of TFE and peptide molecules, it is shown that no single conformation is consistent with the experimental values of the sigma(HF) cross-relaxation parameters. It is argued that the disagreements between observed and expected values of sigma(HF) are the result of formation of long-lived (similar to 0.5 ns) fluoroalcohol-peptide complexes, a conclusion consonant with similar studies of other peptide-fluoroalcohol systems. Complex formation appears to be especially prevalent near the charged amino acid side chains of the hormone.