We have investigated the secretion polarity of human interferon-beta (HuIFN-beta) exogenously expressed in the porcine renal proximal tubule cell line, LLC-PK1. In these cells, stably expressed HuIFN-beta was secreted to the apical and basolateral sides. However, when transiently expressed by apical lipofection, HuIFN-beta was secreted to both cell sides, while basolateral-preferential secretion was seen for basal transfection. Confocal imaging using enhanced green fluorescent protein (EGFP)-tagged HuIFN-beta revealed no difference in the subcellular distribution in either of the chimeric protein-expressing cells examined. These results suggest that the secretion polarity of HuIFN-beta is regulated by a post trans-Golgi network in a cell type-dependent manner.