Using high sensitivity differential scanning calorimetry (HSDSC), the phase transitions of dimyristoylphosphatidylcholine (DMPC) liposomal bilayers and their interaction with the model steroid beclometasone dipropionate (BDP) were found to be dependent on the method of liposome manufacture. Ethanol-based proliposomes produced liposomes having no phospholipid pretransition, a main transition of high enthalpy and a low onset temperature, and a very low incorporation of the steroid (maximum 1 mol%). This was attributed to an alcohol-induced interdigitation of the bilayers, which was not apparently reversed by flushing the liposome dispersion with nitrogen in an attempt to remove ethanol. For liposomes manufactured by thin film or particulate-based proliposome methods, 1–2.5 mol% steroid was optimal for incorporation within bilayers, although the nature of the steroid interaction with the bilayers differed between the two methods. For liposomes manufactured by the thin film method, a higher steroid concentration resulted in a broadened main transition and a reduced melting cooperativity. This suggests that BDP formed separate domains within the bilayers which caused non-ideal mixing and phase separation at 5 mol% steroid. This observation was absent for liposomes generated from particulate-based proliposomes, indicating separate steroid domains were not formed and subsequent non-ideal mixing and phase separation did not occur. In addition, liposomes generated from particulate-based proliposomes showed reduced pretransition and main transition enthalpies. These differences were attributed to the employment of sucrose to manufacture the particulate-based proliposomes. This study has shown that the thermal behaviour of liposomes and their interaction with beclometasone dipropionate were dependent on the method of liposome manufacture. Moreover, particulate-based proliposomes may provide a reasonable alternative to the conventional thin film method in producing liposomes incorporating this steroid.