The effects of the medium on the infrared spectrum of nitrous oxide (N2O) were determined in the antisymmetric stretch region near 2200 cm-1 for solutions of N2O in 38 different solvents at 25 degrees C. The solvents were chosen to reflect the variety of environments potentially available in sites occupied by N2O in nerve and other tissue. Band parameters of overlapping fundamental and hot bands were obtained with deconvolution techniques. Differences in solvent molecule structure had marked effects on both the frequency and the shape of the infrared bands. The fundamental band frequency (v3) ranged from 2215 cm-1 for carbon disulfide to 2230 cm-1 for water. Among the alcohols, v3 increased nearly linearly with increasing dielectric constant. However, solvent parameters that reflect bulk properties of the solvent did not correlate well with v3 over the entire range of solvents studied. Rather short-range specific solute-solvent molecular interactions appear particularly important. In general, v3 increases with the strength and number of dipoles in adjacent solvent molecules interacting with the vibrating dipole of N2O. Half-bandwidths (delta v1/2) ranged from 7.4 cm-1 for carbon tetrachloride to 14.4 cm-1 for hexane. Variations in bandwidth did not correlate in any direct way with solvent polarity, but delta v1/2 did increase with an increase in the conformational flexibility of the solvent molecule, which results in a greater diversity in the immediate environment about the N2O molecules. The observed sensitivity of the N2O infrared band parameters to changes in solvation environment and the appearance of the antisymmetric stretch band at a frequency within a window of relatively low-energy absorption by water makes infrared spectroscopy potentially useful for the characterization of the sites occupied by the anesthetic molecules within lipid, protein, and aqueous components of intact tissue.