Controlled-drug release from electrospun fibers has found important biomedical applications in wound healing, transdermal delivery, and tissue engineering. In this study, poly(D,L-lactide) (PDLLA) was electrospun into ultrafine fibers and loaded with tetracycline (TC) or chlorotetracycline (CTC) as model drugs. The influence of a cosolvent (methanol) at various concentrations was studied regarding physical properties, morphology, and in vitro release profiles of the drugs from the PDLLA nanofibers. Swelling tests in a physiological buffer solution were performed to determine the extent an rate of swelling of the fiber mats. The results showed that for both drugs electrospun fiber diameters decreased with increasing amounts of cosolvent, whereas water contact angles and drug-loading efficiency increased. However, similar in chemical structure, the two drugs exhibited considerably different release mechanisms. The results indicated that the concentration of methanol changed the release profiles mainly based on the morphology of the resultant nanofibers and the polymer/drug/solvent interaction during the electrospinning and drug release process. (C) 2009 Wiley Periodicals, Inc. J Appl Polym Sci 115:1-8,2010