1.The metabolism of the glycolytic end product, octopine, was investigated in vivo in the cuttlefish,Sepia officinalis. Octopine was the major mantle muscle end product produced during hypoxia, exhaustive swimming, or exhaustive swimming followed by hypoxia (muscle octopine rose from 0.2 to 3.7, 8.6, and 13.4 μmol/g wet wt. respectively). Octopine concentration was inversely correlated with muscle glycogen and arginine phosphate concentrations and these substrates were almost completely depleted after swimming to exhaustion. Alanine, α-glycerophosphate, pyruvate, and malate were other, minor end products.2.Blood octopine (0.02 μmol/ml at rest), pyruvate, and alanine concentrations were elevated during hypoxia and during recovery from hypoxia or exercise but not during exercise itself. Maximal blood octopine concentrations were 8-fold higher than resting levels and blood octopine appeared to be derived from the release of muscle octopine into the bloodstream.3.14C-A-octopine (radiolabelled in the arginine moiety: N2-(1-carboxyethyl)[U-14C]L-arginine) was administered intravenously and tissue uptake patterns showed that mantle muscle was relatively poor at the uptake of blood14C-A-octopine while brain and ventricle rapidly concentrated the compound. Parallel experiments in which [U-14C]D-glucose or [U-14C]L-arginine were administered showed that there are distinct tissue specific uptake patterns for each of the three radiolabelled compounds.4.The tissue breakdown of14C-A-octopine taken up from the blood to form14C-arginine was found to be 0, 6, 32 and 20% respectively for mantle muscle, gill, ventricle, and brain. When delivered by specific injection into mantle muscle or brain,14C-A-octopine oxidation was 5% and 40% respectively after 20 min under resting, aerobic conditions.5.The data indicate that while mantle muscle readily produces octopine as a glycolytic end product, the tissue has little capacity for the oxidation of octopine. Muscle octopine appears to be released into the bloodstream and can be readily taken up by other tissues. The pyruvate moiety of octopine could be oxidized as an aerobic substrate by the Krebs cycle in tissues such as brain and ventricle with the arginine moiety being recycled to the muscle. The possible existence of a modified Cori cycle, to make use of octopine as a gluconeogenic substrate, is discuss