The three-dimensional structure determination of a medium-size natural product often requires recording time-consuming 2D ROESY spectra. When the amount of sample available is limited, a series of suitable 1D selective ROESY experiments provide the same information using much less experimental time. The setup and the choice of 1D selective ROESY experiments are critical to obtain reliable results. Often, organic and natural products chemists overlook these aspects and do not make the most effective possible use of existing ROESY experiments. We propose a 1D selective ROESY experiment tailor-made for investigating the structure of natural products. The experiment has been tested on a sample of cyclosporine, and analyses of the spectra demonstrate that the experiment provides clean spectra, allowing reliable cross-peak integration while maintaining high sensitivity. In addition, the experiment does not need a sample-specific setup and can be used as it is starting from standard parameters set by inexperienced users as well as under automated conditions.