We have shown that 16, 16 dimethyl PGE2 augments mucosal hyperplasia following massive small bowel resection in the rat. Likewise restricting dietary linoleic acid inhibits adaptation. PG may therefore be an important mediator of adaptation. We studied the effect of aspirin (ASA) inhibition of mucosal PG synthesis on mucosal adaptation following 70% proximal jejunoileal resection in 160g male Sprague-Dawley rats. Sixteen of 27 resected and 8 of 16 sham operated rats were given ASA 20mg/kg subcutaneously every 8 hours for 11 days following surgery; the remainder were given vehicle. Animals were fed a purified diet containing 5% linoleic acid ad lib. After 14 days, ex vivo mucosal PGE2, PGF2α, and thromboxane B2 synthesis, and mucosal weight, protein, DNA, and maltase levels were determined. PG synthesis rates are shown below Mean ± SEM (ng/g tissue/min.).Despite marked inhibition of mucosal PG synthesis (P <.01) animals receiving ASA had comparable mucosal weight, protein, and maltase levels, when compared to controls. Endogenous PG may not be important in mucosal adaptation.