The permeability of drugs across the Xenopus pulmonary membrane and the effects of various additives on transport of drugs and electrophysiological parameters were examined using an in vitro Ussing chamber technique. Insulin, phenol red and FITC-labeled dextrans (FDs) with various molecular weights were chosen as model drugs. Additives used in this study were N-lauryl-β-D-maltopyranoside (LM), sodium glycocholate (NaGC), sodium salicylate (NaSal), disodium EDTA (EDTA), soybean trypsin inhibitor (STI) and bacitracin. The permeability of drugs gradually decreased with increasing their molecular weights. There exists a good correlation between the logarithm of molecular weights of drugs and the logarithm of apparent permeability coefficients of drugs. The permeability of phenol red and insulin significantly increased by LM. However, other additives showed no significant effect. Transepithelial electrical resistance (TEER) was markedly decreased after the addition of LM. On the other hand, a slight decrease in the TEER value was observed in the presence of NaGC. These findings suggest that this method is useful for estimating the transport characteristics of drugs across the pulmonary membrane.