Secretion of HCO₃^– by airway submucosal glands is essential for normal liquid and mucus secretion (2). Since the liquid bathing the airway surface is acidic, we proposed that the surface epithelium may acidify HCO₃^–-rich glandular fluid (1). We showed that isolated distal bronchi, containing both glandular and surface epithelium, can both acidify and alkalinise their lumens (2). The aim of this study was to investigate the effect of forskolin on acid and base equivalent secretion in these airways. Porcine distal bronchi were isolated from pigs humanely killed with an overdose of sodium pentobarbital, cannulated in a bath containing HCO₃^–-buffered solution and perfused with similar solution, in which NaCl replaced NaHCO₃. This solution was lightly buffered (0.6 mM pH unit^-1) with KH₂PO₄ and NaOH to pH7, gassed with 100 % O₂ to eliminate dissolved CO₂ and stirred vigorously. The pH of this circulating luminal solution (10 ml) was monitored continuously. As previously shown (2), upon perfusion through the airway lumen pH of the circulating solution (pH_Lumen) initially fell, by 0.055 ± 0.005 pH units (means ±S.E.M., n = 7). Pretreatment (3min) with forskolin (10μM) had no effect on this acidification (0.061 ± 0.008 pH units, P > 0.05, Student’s paired t test used throughout). After this initial acidification pH_Lumen became relatively stable with a trend to alkalinisation (3). Addition of forskolin at this stage had no effect on pH_Lumen (basal rate of alkali secretion 0.34 ± 0.13μmoles hr^-1, after forskolin addition 0.36 ± 0.11μmoles hr^-1, n=9, P > 0.05). In contrast the glandular secretagogue acetylcholine (ACh) stimulates alkalinisation (2). Addition of bumetanide, to block Cl^– secretion, stimulates HCO₃^– secretion in these airways and augments the response to ACh (2). Bumetanide (100μM), however, did not alter the response to forskolin (pre-forskolin alkalinisation 0.57 ± 0.11μmoles hr^-1, after forskolin 0.59 ± 0.02μmoles hr^-1, n=4, P > 0.05). These results suggest that increases in intracellular cAMP do not control the secretion of acid and base equivalents in these airways. To further investigate these findings, the effect of forskolin on the ACh-evoked secretion of HCO₃^– was studied. As previously described (3), ACh stimulated secretion of HCO₃^– (0.36 ±0.05 μmol hr^-1). This was significantly inhibited (34 ± 12 %, n=7, P<0.05)) by prior treatment with forskolin. Thus, whilst cAMP-mediated intracellular signalling pathways may not themselves control acid and base secretion in these airways, they seem to modify the effect of ACh on HCO₃^– secretion.