In the present study the disposition of α-trinositol in rats, with special emphasis on its metabolism, was investigated. The drug was administered as an intravenous bolus dose (18.2 μmol/kg) immediately followed by a short term intravenous infusion (48.8 μmol/kg/h) of [ 3H]α-trinositol over 1.5 h. In the plasma samples, only unchanged α-trinositol, InsP 2, InsP 1, inositol and water were detected which indicates that during metabolism of α-trinositol in the rat only these metabolites are formed. The plasma concentration–time profile of α-trinositol showed a very fast decline following the cessation of the intravenous infusion, which probably is due to rapid metabolism and therefore a relative high total clearance of the drug, 23±4.3 ml/min/kg. The volume of distribution at steady state is 3.5±1.5 l/kg in the rat. To gain further insight into the metabolism of α-trinositol, we have also examined the possible metabolism by blood cells using intact human platelets, platelet homogenates, intact human neutrophils and also α-trinositol incorporated into human platelets using reversible electropermeabilization. Intact platelets and neutrophils showed little ability to metabolize α-trinositol when measured over a one hour incubation period. Platelet homogenates also showed little ability to metabolize α-trinositol under conditions where inositol 1,4,5-trisphosphate was rapidly metabolized to both inositol bisphosphate and inositol tetrakisphosphate. When α-trinositol was encapsulated into human platelets during reversible electropermeabilization significant metabolism was observed, with the main metabolite being InsP 1. We have also examined α-trinositol metabolism with alkaline phosphatases from bovine intestinal mucosa, kidney and liver. The intestinal enzyme showed extensive dephosphorylation of α-trinositol to Ins(1,2)P 2 and Ins(2)P 1 The kidney and liver enzyme showed slower dephosphorylation of α-trinositol with the end product being Ins(1,2)P 2.