The clinical pharmacokinetics of ergotamine, dihydroergotamine, ergotoxine, bromocriptine, methysergide, and lergotrile are reviewed. Generally the new radioimmunoassay methods have partially resolved the problems involved in determining some of these ergot derivatives in biologic fluids after the low doses used clinically. However, our present knowledge of their pharmacokinetics is limited and much work remains to be done in this area. Many cases show a great difference between results produced with a radioactive drug and with radioimmunoassay. The longer half-lives measured by using a radioactive derivative are apparently due to the many metabolites of ergot alkaloids. However, we still do not know the clinical importance of these metabolites. For instance, the amount of dihydroergotamine reaching the systemic circulation remains below 1% (radioimmunoassay), but according to studies performed with a radioactive derivative the absorption quotient is about 30%. Further studies are needed to resolve the problem of an apparently high "first-pas" metabolism of this and other ergot alkaloids in the liver or gastrointestinal mucosa.