A method for the quantitative analysis of gas-phase infrared spectra is described in which calibration spectra are calculated from a database of absorption line parameters rather than measured in a real spectrometer. The synthetic calibration spectra are computed with the use of the program MALT (Multiple Atmospheric Layer Transmission), including environmental (pressure, temperature, pathlength, etc.) and instrumental (resolution, line shape, wavenumber shift) effects in the calculation, so that the calculated spectra closely approximate real measured spectra. The synthetic calibration spectra are then used in quantitative analysis as if they were real spectra. In conventional laboratory studies, the method circumvents the need for time-consuming collection of large sets of laboratory calibration spectra often required when many absorbing gases must be analyzed. It is particularly useful in long open-path and solar FT-IR spectroscopy when no sample cell is available for recording calibration spectra. Examples are presented from conventional laboratory spectra in a closed-cell, open-path FT-IR spectra used to determine trace gas fluxes in an open field, and solar absorption spectroscopy using ground-based FT-IR spectrometers.