1. We have investigated the effects of various potential inhibitors on flow-dependent K+ permeability (PK) of single perfused mesenteric microvessels in pithed frogs. 2. Neither superfusion with a nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (10 or 100 micromol l-1), nor the addition of indomethacin (30 micromol l-1) to both perfusate and superfusate reduced the positive correlation between PK and flow velocity (U). 3. In the presence of agents known to raise intracellular levels of adenosine 3',5'-cyclic monophosphate (noradrenaline, 8-bromo-cAMP and a combination of forskolin and rolipram) the slope of the relation between PK and U was no longer significant, so that PK was no longer flow dependent. 4. These results confirm that the flow dependence of PK is a biological process and not an artefact of measurement and suggest a role for intracellular cAMP rather than nitric oxide or prostacyclin in the flow-dependent modulation of PK in frog mesenteric microvessels.