Rizatriptan nasal spray was developed to achieve fast a high effectiveness and to overcome limitations associated with oral formulation. The objective of this study was to investigate the pharmacokinetics and tolerability of a rizatriptan nasal spray compared with an oral formulation in a two treatments, two periods, randomized crossover design. At each phase, each subject received 5 mg rizatriptan as a nasal spray or an oral tablet. Plasma concentrations of rizatriptan were determined by HPLC. Rizatriptan was absorbed more rapidly following nasal spray with detectable plasma concentrations 5 min after dosing. There was no statistically significant difference for AUC or Cmax values between the nasal spray and the oral tablet. The relative bioavailability of nasal formulation to oral formulation was 96%+/-16%. All the formulations were well tolerated and adverse events were generally of short duration and of mild intensity. Thus, rizatriptan nasal spray offers more rapidly absorption compared to the oral route, which may be particularly beneficial to those patients who have gastrointestinal disturbances during their migraine attack or who have difficulty in swallowing a tablet.