Glycosphingolipids (GSLs) are physiological membrane components known to modulate various cellular functions. In order to study their influence on basophil mediator release washed leukocytes obtained from allergic asthmatics and nonatopics were preincubated with varying concentrations of different GSLs. Cells were washed and stimulated with anti-IgE, allergen, and calcium ionophore A23187. None of the GSLs induced mediator release by itself. Preincubation with the acidic gangliosides GM2, GM3, and GD1a significantly enhanced the release of both mediators when stimulated with anti-IgE or allergen but not with calcium ionophore A23187. Highest enhancement was seen with ganglioside GM2. Mediator release was higher in asthmatics than in nonatopics. The acidic galactosylceramide-sulfate (sulfatide) showed a significantly enhanced mediator release as well, whereas the neutral GSLs lactosyl ceramide and asialo GM2 did not influence mediator release. It is concluded that IgE receptor-dependent mediator release could be modulated by acidic GSLs.