The present study compare oral and rectal delivery routes of a salmonid gonadotropin releasing hormone analogue (sGnRH-a) + dopamine D-2-receptor antagonist, pimozide (Pim), with parenteral administration. In addition, the effect of co-administration of absorption enhancers and peptidase inhibitors were evaluated. Responsiveness to the treatments was examined using GtH II release. Ten micrograms sGnRH-a and 5 mg/kg of Pim per kg fish bw were used in different formulations and routes of delivery. A mixed micellular intestinal absorption enhancement formulation, consisting of oleic acid and a polyoxyethylenesorbitan (Tween), strongly augmented GtH II release stimulated by sGnRH-a + Pim. GtH II release following treatment did not differ from that obtained after intraperitoneal injection of these drugs. In comparison with the saline control or with intraperitoneal injection, the oral and rectal administration of sGnRH-a + Pim without intestinal absorption enhancement was not effective in stimulating GtH 11 release. The addition of the enzyme inhibitor, Na(2)EDTA or chicken egg trypsin inhibitor to this formulation was only moderately effective in increasing circulating GtH 11 levels. Among different Tweens, preformulated with oleic acid in a mixed micellular absorption enhancer for rectal delivery of sGnRH-a at a dose of 20 mug/kg bw in pimozide pretreated carps, Tween 20 and Tween 40, resulted in the highest systemic GtH II levels. (C) 2002 Elsevier Science B.V. All rights reserved.