After single 0.5-mg nad 1.0-mg i.v. injections, dihydroergotamine, as measured by a radioimmunoassay, disappeared quickly from the plasma of beagles, with a mean alpha-phase half-life of 1.32--1.91 min. This explains its effect of rapidly lowering the temperature of the ear of the dog. Its short beta-phase half-life (mean, 40.79--70.13 min), a moderately low volume of ditribution at beta-phase (mean 1.50--3.46 L/kg) and a rather high plasma clearance value (mean, 311.67--587.88 ml/min) indicate a rapid elimination of the drug from the organism. The 24-hr urinary excretion of dihydroergotamine was 2.7% of the 0.5-mg i.v. dose and 2.3% to 3.1% of the 1.0-mg i.v. dose. A measure of the amount of a 7.5-mg p.o. dose of the drug reaching the systemic circulation was obtained from the ratio of the area under the plasma curve after p.o. administration to that after i.v. administration, corrected for the different amounts given by the two routes. Only 1.2--1.4% of the 7.5-mg p.o. dose of dihydroergotamine reached the systemic circulation. There were no significant differences in the plasma levels of dihydroergotamine after a single dose of the two preparations tested, Vasogin (Leiras) and Orstanorm (Sandoz), given either by the oral or intravenous route.