Abstract The accuracy of near-infrared spectroscopy (NIRS) when applied to high-moisture samples (i.e., silages) does not match that with dried materials. Previous work showed that the presence of water could cause shifts in the spectra of organic compounds, the degree of which depended on the material and the water concentration. For some solids, such as sugars, large spectral changes occur on dissolution. The objective of this study was to determine the effect of pH, ionic strength, and physical state on the NIR spectra of model compounds. The results show that pH has large effects on the spectra of amines and acids but little if any on the spectra of ketones, alcohols, and sugars. The spectra of peptides and proteins also were pH dependent, but that of cellulose was not. Ionic strength differences (deionized water vs saturated NaCI solution as the diluting media) had only minor or no effect on the spectra of the materials studied. The effect of physical state was far more complicated; the spectra of freeze-dried glucose and glycine were different from that of the crystalline forms, but the spectrum of serine was not. The spectra of molten compounds often appeared like those of solutions. These results, in agreement with earlier work, may explain the poorer performance of NIRS with wet materials compared with dry samples. They also have serious implications for the analysis of dried samples, if pH, ionic strength, or drying method varies among samples.