The effects of luminal glucose on transepithelial Na+ and fluid transports were investigated in rat lungs. Two preparations were used: isolated, perfused lungs and lungs in situ perfused with blood (cross-circulations), a situation more comparable to that existing in vivo. Unidirectional (efflux from air spaces, J(out)) and net (Jnet) Na+ fluxes and fluid absorption from air spaces were estimated in lungs filled with bicarbonate-buffered solutions containing 10 mmol/l of either mannitol, glucose or alpha-methyl-D-glucopyranoside, or 0.1 mmol/l phlorizin in the presence of glucose. In the presence of mannitol J(out) was estimated to be 7.8 +/- 1.02 pmol cm-2 s-1 in isolated lungs and 9.2 +/- 0.97 pmol cm-2 s-1 in lungs in situ, and Jnet 1.0 +/- 0.33 and 2.5 +/- 0.35 pmol cm-2 s-1, respectively. When glucose replaced mannitol J(out) (+ 30% + 40%), Jnet (+200% + 300%) and fluid absorption (+ 100% + 400%) were enhanced in both preparations. Substituting methyl glucoside for mannitol increased Na+ and fluid absorption rates to the same extent as glucose. Phlorizin, in the presence of glucose, reduced Na+ and fluid transports to values similar to those observed in the presence of mannitol. These changes did not result from modifications of the paracellular permeabilities (assessed with [3H]mannitol).(ABSTRACT TRUNCATED AT 250 WORDS)