The pharmacodynamics, pharmacokinetics, metabolism, and excretion of 14C-sumatriptan have been studied in the beagle dog following administration by the intranasal and other routes. The pharmacological response which was monitored, an increase in carotid arterial vascular resistance, correlated with the plasma levels of unchanged sumatriptan following intranasal, intravenous, or intraduodenal administration to the anaesthetised dog. The pharmacokinetics and metabolism of sumatriptan were then confirmed in conscious male and female dogs. Intranasal administration of 14C-sumatriptan resulted in rapid absorption of part of the dose. The overall bioavailability of sumatriptan was 40-50%. Sumatriptan was eliminated from plasma with a half-life of 1.5 or 1.9 h after intravenous or intranasal dosage respectively. Radioactivity was largely excreted in urine (up to 75% of the dose) with small amounts in the bile and faeces after intravenous and intranasal dosing, as sumatriptan and a major metabolite. The results from these studies suggest that intranasal administration provides a viable method for delivering sumatriptan to the systemic circulation.