OBJECTIVE: To study the effect of endogeneous ganglioside (GS) on the adhesion of LA-N5 neuroblastoma cells to collagen. METHODS: LA-N5 cells were cultured in the presence of D-threo 1-phenyl 2-decanolamino 3-morphinoline 1-propanol (D PDMP), an inhibitor of glucosylceramide synthase. The adhesion of the LA N5 cells to immobilized collagen was tested. RESULTS: After 6 days, endogenous GS was reduced by 98%. No change in the cell morphology, viability, proliferation rate or percentage of apoptotic cells was observed. The adhesion to collagen of cells exposed to D PDMP was reduced by 65% compared to the control LA-N5 cells: OD 5700.07±0.01 vs 0.21±0.030(P<0.01). When GS depleted cells were pre incubated in a conditioned medium collected from the control cells, the adhesion to collagen was restored and was comparable to that of the control cells (P>0.05). Similarly, the pre incubation of GS depleted cells with purified tumor GS GD-2, the most abundant GS in LA-N5 cells, restored adhesion. CONCLUSIONS: Endogenous tumor GS regulates neuroblastoma cell adhesion to collagen, suggesting that it may play a role in tumor cell migration, invasion and metastasis.