The relationship between the P-glycoprotein-mediated vinblastine secretion and cell-swelling activated Cl - secretion (conductance) in intact epithelial layers of human colonic adenocarcinoma T 8 4 cells has been investigated. Whereas vinblastine secretion is effectively inhibited by 100 μM 1,9-dideoxy-forskolin, volume-stimulated Cl - secretion is unaffected. In contrast, 100 μM 4,4'-diisothiocyanostilbene-2,2'disulphonic acid (DIDS) inhibited the volume-stimulated Cl - secretion, but was without effect upon transepithelial vinblastine secretion. In addition, it was noted that some epithelial layers failed to express a volume-stimulated Cl - secretion but maintained a normal level of secretory vinblastine flux.