The pharmacokinetics of dihydroergotamine was studied following a 1.5-mg subcutaneous dose of the mesylate salt in six healthy volunteers. Plasma and urine dihydroergotamine, determined using a specific radioimmunoassay, were simultaneously fitted to equations consistent with a two-compartment open model. The drug was rapidly absorbed from the injection site; peak plasma concentrations of 3-8 ng/ml were observed within 15-45 min of dosing. Half-lives for the rapid and slow phases of decline in plasma dihydroergotamine were 0.95 and 7.26 h, respectively. The overall volume of distribution was 14.6 l/kg. The plasma clearance and renal clearance values were 1814 and 91 ml/min, respectively, indicating that 5% of the dose was excreted unchanged in the urine. Comparison of the results of the present study to published data confirmed that dihydroergotamine is eliminated from the body predominantly by metabolism.