The effects of arachidonic acid and arachidonoyl CoA on the catabolism of prostaglandin E2 in a 105000 x g supernatant fraction from rabbit kidney cortex were examined. Arachidonic acid reduced the 15-hydroxy prostaglandin dehydrogenase activity by 50% at 20 microM, while arachidonoyl CoA showed weak inhibition for the enzyme activity (15% at 20 microM). However, arachidonoyl CoA strongly inhibited the prostaglandin delta 13 reductase activity, the concentration required for 50% inhibition being about 3 microM. The dehydrogenase inhibition by arachidonic acid was non-competitive with regard to NAD+ and prostaglandin E2, respectively. Arachidonoyl CoA was also a non-competitive inhibitor for the reductase with regard to NADH and 15-keto prostaglandin E2, respectively. These results suggest that arachidonic acid and arachidonoyl CoA can be important modulating factors in prostaglandin catabolism by the kidney cortex.