The LLC-PK1 pig kidney-derived cell line is morphologically and functionally heterogeneous. We have clonally derived three sublines that differ in their response to calcitonin and in their ability to form domes. The three clones were analyzed for their basal and hormonally induced plasminogen activator production. In contrast to the D + Sc clone, in which calcitonin induced a greater than 100-fold increase in plasminogen activator synthesis, the D + Rc clone did not respond to the hormone; this was related to a deficiency of the cells in calcitonin binding. Transepithelial electrical resistance measurements revealed a direct correlation with the capacity of the cells to form domes; in one of the isolated clones (D-), the lack of dome formation coincided with a low electrical resistance; the D + Sc clone, in which all single cell-derived colonies formed domes, showed a higher electrical resistance than that developed by the original cell line. Thus the LLC-PK1 clones provide a useful in vitro model for the study of epithelial properties.