The physico-chemical properties of biodegradable polylactide-co-glycolide (PLGA) microspheres containing the peptide salmon calcitonin (sCT) were affected by the processing parameters. The microsphere size increased with an increase in the viscosity of the polymer solution. Concentration of methanol and peptide in the dispersed phase had the most discernible effects with the combination causing external and internal porosity. Increasing sCT in the presence of methanol increased the surface area and porosity. The surface area also increased as the molecular weight of the polymer was decreased. At higher ratios of the dispersed phase volume to the continuous phase volume, the surface area and surface porosity were higher and the particle size was lower. Thus, the physico-chemical properties of the microspheres can be easily altered by varying the processing parameters allowing formation of microspheres with a range of properties. The microspheres may be used to evaluate the relationship between the properties and ultimate in-vivo performance.