Two commercial brands of microcrystalline cellulose, the widely used Avicel(R) PH-101 and the newly available Pharmacel(R) 101, were compared for aqueous extrusion-spheronization of a model mix with lactose. Based on the results of multi-level experiments employing pellet size analysis by sieving and sphericity determination by image analysis, Avicel was shown to be less adversely affected by variation in added water or speed of spheronization. Physicochemical testing of powder samples from both brands was carried out using laser particle size analysis, density determinations, differential scanning calorimetry and X-ray diffraction studies. The results indicated that the improved ease of processing with Avicel may be related to its smaller particle size with less aggregates, improved flow, lower depolymerization temperature range and absence of traces of cellulose II in its cellulose I content.