The gastroprotective properties of GM1-ganglioside, an indigenous component of epithelial cell membrane, was investigated. The experiments were conducted with groups of rats with and without indomethacin pretreatment. The animals received intragastrically either a dose of GM1 as emulsion in 5% gum arabic or vehicle alone, followed by ethanol given at various time intervals up to 3 h after the GM1. The animals were sacrificed 30 min after the ethanol dose and their gastric mucosa subjected to macroscopic and histologic assessment, and physicochemical measurements. In the absence of GM1, ethanol caused extensive gastric hemorrhagic lesions which were significantly reduced by pretreatment with GM1 at dose as low as 70 micrograms/100 g body weight. Removal of sialic acid from GM1 led to the loss of gastroprotection. Furthermore, the effect of GM1 was not thwarted by indomethacin. The maximal protection was achieved 1 h following GM1 dose and this protective effect persisted at least 2.5 hr. The results of physicochemical measurements revealed that GM1 was capable of preventing the detrimental effect of indomethacin on the adherent mucus gel dimension, and on its content of sulfo- and sialomucins, protein, and phospholipids. The effects brought by GM1 were also accompanied by a significant (40-60%) increase in mucus gel viscosity, hydrogen ion retardation capacity (35-46%) and hydrophobicity (70-94%). The results indicate that the gastroprotective action of GM1 occurs through the enhancement of the physicochemical characteristics of the mucus layer, and does not appear to be mediated by endogenous prostaglandins.