It has been suggested that detergent-resistant membranes (DRMs), also known as lipid rafts, are involved in vectorial transport of proteins to the apical surface. In this report we use Madin-Darby canine kidney (MDCK) cells expressing the apically secreted Cl-esterase inhibitor, the non-sorted antithrombin or chimeras of serpins to study the possible connection between DRM association and apical targeting of secretory proteins. We found newly synthesised C1-esterase inhibitor associated with DRMs in MDCK cells, whereas antithrombin was not. However, two chimeric proteins, secreted mainly from the apical membrane, do not associate with DRMs. Based on these observations we suggest that apical targeting and association with DRMs are two independent events for secretory serpins. (C) 2002 Elsevier Science (USA). All rights reserved.