The effects of some inhibitors of 15-hydroxy-prostaglandin dehydrogenase (PGDH) have been studied on the inactivation of prostaglandin E2 (PGE2) and 16, 16-dimethyl PGE2 in rat isolated lung. 2. Bioassay was used to show that the inactivation of PGE2 and its methyl analogue, was inhibited by frusemide (10(-3) M), N-ethyl maleimide (10(-5) M) and 5,5'-dithio-bis-2-nitro-benzoic acid (10(-2) M), but not by caffeine (2.5 x 10(-3) M). 3. The efflux of radioactivity from lung following injection of [14C]-PGE2 was faster in lungs treated with frusemide, N-ethyl maleimide or bromcresol green, than in untreated lungs. 4. Caffeine (10(-3), 10(-2) M) did not change the rate of 14C-efflux from lungs following injection of [14C]-PGE2. 5. From these results it is concluded that those PGDH inhibitors that prevented prostaglandin inactivation in isolated lungs did so by inhibiting uptake of prostaglandin rather than by inhibiting PGDH.