Recrystallization of theophylline was carried out from an ethanol:methylene chloride solution, using carbon dioxide as antisolvent. The two variants of the technique - bubbling CO2 (GAS) or spraying the solution (SAS) - were investigated in order to explore the effect of specific conditions on physical (particle size distribution) and chemical (crystalline form) attributes of the product. The particle size analysis showed that particles were almost insensitive to the operating conditions in the GAS mode. The analysis of phase behavior revealed that precipitation occurred for a CO2 mole fraction above 0.63 and when the CO2-solvent system crossed the L-V coexistence line, i.e. when the bi-phasic mixture merged as a single phase. In the SAS mode, the vicinity of the mixture critical point allowed for reducing the mean size and the size distribution as well. Most X-ray diffraction patterns of CO2-processed powders were found to exhibit new peaks, with an occurrence influenced by process version, pressure and temperature. The comparison with theoretical patterns obtained through various crystal modifications indicated that the new patterns were attributable to a change of the symmetry group rather to a textural effect. Finally, SAS mode was proven to be more efficient at producing narrower and smaller particle size than GAS especially when co-flow injectors were used. (C) 2011 Elsevier B.V. All rights reserved.