A novel complex of salicylic acid (SA) and gamma-cyclodextrin (gamma-CD) was obtained via the sealed-heating method. The influence of the water content of gamma-CD on the complex formation with SA by sealed-heating process was investigated. Quantitative determination of SA revealed that sealed-heated samples of SA and gamma-CD with low water content (0.8-5.4%) formed the SA/gamma-CD = 2:1 complex, while the samples with high water content (8.5-11.5%) formed the SA/gamma-CD = 4:1 complex. The molecular arrangements of gamma-CD in 2:1 and 4:1 complexes were determined by powder X-ray diffraction measurements to be in monoclinic-columnar and tetragonal-columnar forms, respectively. The results of infrared spectroscopy and (13)C solid-state NMR measurements showed that two types of SA molecules resided in the 4:1 complex, whereas only one type of SA molecules existed in the 2:1 complex. The obtained 2:1 complex was assumed to contain two SA molecules per one gamma-CD, with the SA molecules existing in the intermolecular spaces formed by the gamma-CD columns. In the case of the 4:1 complex, two SA molecules were incorporated into the intermolecular spaces while the other two SA molecules were included within the gamma-CD cavity.