Two different types of soft alkyl ether prodrugs incorporating ethyleneoxy groups into the promoiety have been synthesized for a model phenol (acetaminophen, APAP): alkyloxycarbonyloxymethyl type (AOCOM) and N-alkyl-N-alkyloxycarbonyl-aminomethyl type (NANAOCAM). The solubilities in isopropyl myristate, S(IPM), and water, S(AQ), partition coefficients between IPM and pH 4.0 buffer, K(IPM:4.0), and the delivery of total species containing APAP through hairless mouse skin from IPM, J(MMIPM), have been measured for the prodrugs. The J(MMIPM) values were accurately predicted by the Roberts-Sloan (RS) equation. Only modest increases in JMMIPM were realized (about 1.4 times) by each type. The only prodrug that was more water soluble and more lipid soluble than APAP did not improve J(MMIPM) of APAP. This result may be due to the strong association of water molecules with the ethyleneoxy groups, and especially the triethyleneoxy derivative, which dramatically increases the molecular weight and depresses J(MMIPM).