1. Adrenaline (5 uM) stimulated a K+ secretory current by 2-2 ftequiv h-' cm2 in isolated guinea-pig distal colonic epithelium. This secretory activity was inhibited entirely by addition of the loop diuretic bumetanide to the serosal solution. On-going K+ uptake via the absorptive pathway was unaltered by these changes.2. Prostaglandin E2 (PGE2, 2 /M) stimulated electrogenic K+ secretion and Cl-secretion by 3 0 and 3-6 ,tequiv h-cmM2, respectively. Serosal addition of bumetanide completely inhibited this K+ secretion but blocked only -70% of Cl-secretion. The bumetanideinsensitive Cl-secretory current was dependent on the presence of Cl-and HC03-in the bathing solutions. 3. Stimulation of electrogenic K+ secretion by PGE2 occurred with a half-maximal concentration of 4 nm, an affinity -300 times higher than that for stimulation of Clsecretion by PGE2.4. Forskolin (10 AM) stimulated Cl-secretion by 4-9 tequiv h-' cm2. The apparent K+ secretory rate was increased by only 1-5 ytequiv h-1 cm2. A bumetanide-insensitive shortcircuit current (Isc) was apparent and of the same size as that stimulated by PGE2.5. Addition of the Ca2+ ionophore A23187 (10 fSM), in the presence of indomethacin (1 /SM) to reduce prostaglandin production, inhibited the K+ absorptive pathway by 40% and concurrently stimulated a small rate of electrogenic K+ secretion. 6. Active K+ absorption was inhibited by the addition of ouabain, omeprazole or SCH28080 to the mucosal solution. Both omeprazole and SCH28080 also stimulated a small negative Isc, consistent with electrogenic K+ secretion. 7. Association of K+ absorption, K+ secretion and Cl-secretion is indicated by similarities in transport mechanism and by secretagogue regulation. In particular, maximal rates of K+ secretory current require uptake via apical membrane K+ pumps. Such interrelations support a common cellular locus for these ion transport pathways.Potassium transport across the epithelium lining mammalian distal colon occurs via both active secretory and active absorptive pathways (Halm & Frizzell, 1991). Regulation of these two oppositely directed transport processes permits a range of net flows. Active flow of K+ through the secretory pathway proceeds via a cellular mechanism similar to that for Cl-secretion ; uptake of K+ occurs through Na+-K+ pumps and Na+-K+-2Cl-cotransporters in the basolateral membrane with K+ exit from the cell through channels in the apical and basolateral membranes. The ratio of these K+ conductances together with K+ electrochemical gradients determine the rate of K+ secretion. A cellular mechanism for active K+ absorption has not been resolved as clearly.