Pharmacokinetics for one growth hormone secretogogue (NNC 26-0722), but not for another (NN703), differ between dogs in estrus or anestrus. We examined if the differences could be mimicked by administering estradiol during anestrus and if there was a relationship with rates of small intestine absorption. Pharmacokinetics for oral doses of NN703 (1.0-1.6 mg kg(-1)) did not differ among dogs in estrus, anestrus, or anestrus and given estradiol for 1 week (days 1, 3, and 6; 40 micro g kg(-1)), whereas plasma concentrations of NNC 26-0722 increased from undetectable in untreated, anestrus dogs to several hundred nanograms per milliliter in dogs given estradiol, with maximal concentrations measured 5 min after oral dosage. Estradiol treatment increased small intestinal absorption of NNC 26-0722 by 100% (P<0.05), but did not increase absorption of NN703, and caused a 64% increase in carrier-mediated glucose transport at 50 mmol l(-1) (P<0.05) due to increased densities of transporters. These findings indicate estrus and estradiol enhance absorptive functions of the dog proximal small intestine and can affect pharmacokinetics for some orally administered drugs.