Ultrafine fiber mats of hydroxypropyl methyl cellulose phthalate (HPMCP) were successfully electrospun and explored as drug delivery vehicles using erythromycin as a model drug. The morphology of the electrospun fiber and the drug release process in the artificial gastric juice and in the artificial intestinal juice were investigated. With the same drug-to-matrix ratio (HPMCP/erythromycin = 9/1.), all the fibers were electrospun into a tape-like or ribbon shape and the average fiber diameter (AFD) was increased with the HPMCP concentration. Because of the pH-sensitive property of HPMCP, erythromycin was released from the erythromycin-containing electrospun HPMCP fiber mats by a slowly diffusion process in the artificial gastric juice, while it was released in nearly first-order kinetics in the artificial intestinal juice because of the first-order kinetics dissolution of the HPMCP fibers in the artificial intestinal juice. And the rate of erythromycin released in the artificial intestinal juice was about more than 2.5 times faster than that in the artificial gastric juice. The diameter of the fibers plays an important role on the rate and the total amount of the drug released both in stomach and in intestine, the rate and the total amount of the drug released decreasing with increasing AFD. (c) 2007 Wiley Periodicals, Inc.