We studied the mode of uptake of exogenous sialoglycolipids with a permanent mouse cell line (Clone-1D) and compared the cell association of ganglioside II3 NeuAc-Gg4 Cer with that of a synthetic one-C18-hydrocarbon-chain ganglioside analogue (desphingo-G1-stearamide). In contrast to monolayer cultures, Clone-1D cells in suspension bind both sialo-glycolipids rapidly and independently of time and temperature (4 degrees/37 degrees C) of incubation. Three modes of cell association were distinguished: 1) a serum-and serum albumin-sensitive association; 2) a trypsin-sensitive association and 3) a serum- and trypsin-insensitive association. Inhibition of pinocytosis by deoxyglucose/sodium azide did not significantly influence cellular uptake or release of exogenous ganglioside. In monolayer culture, Clone 1D cells in M-phase associate more ganglioside than randomly growing cells. This may explain in part the inhomogeneous cellular distribution of ganglioside binding. In contrast, uptake of desphingo-G1 -stearamide by cells in mitosis equalled that bound by control cells.