Sumatriptan is a selective agonist of 5HT1 (1B/1D) receptors, which has proved to be effective and safe for the acute treatment of migraine attacks. Nevertheless, its use by migraine sufferers is still limited and some patients consider adverse reactions related to sumatriptan, especially chest symptoms, unacceptable even if not serious. Moreover, in clinical trials, almost one third and one sixth of patients, respectively, fail to experience headache relief either after oral or after subcutaneous sumatriptan administration. Our aim was to verify whether differencies in sumatriptan pharmacokinetics could explain non–response and/or adverse drug reactions. Sumatriptan levels were determined by HPLC with electrochemical detection. Pharmacokinetic parameters were calculated using a computer program (PK Solutions 2.0; non compartmental Pharmacokinetics Data Analysis). After oral administration, sumatriptan is rapidly absorbed and sometimes displays multiple peaks of plasma concentration. This “multiple peaking” gives rise to considerable inter–subject variability in the time of reaching maximum plasma concentration. Pharmacokinetic parameters of sumatriptan, both after oral and subcutaneous administration, were similar in the three patient groups. Blood pressure and heart rate did not show any significant differences between groups. Pharmacokinetic parameters and bioavailability of sumatriptan did not seem to be correlated either to the lack of efficacy or the appearance of side effects. These results could depend on the limited number of patients studied.