Differential scanning calorimetry was used to investigate the thermotropic behaviour of various gangliosides differing in size and in the net negative charge. It was found that the number and the position of the negative charges in the headgroup region influence strongly the phase transition profiles. Interaction of GM1 ganglioside with egg phosphatidylcholine or cholesterol was also investigated. GM1 is completely miscible with egg phosphatidylcholine, giving only one transition peak at all ratios of the two components, implying that when gangliosides are in a more fluid lipid environment in biological membranes they will be randomly distributed. Interaction with cholesterol decreases the enthalpy of melting of the ganglioside. The decrease in enthalpy reaches a plateau at about 30 mol% cholesterol, suggesting a lower affinity of cholesterol for gangliosides than for sphingomyelin.