We studied target volume coverage and normal tissue sparing of serial tomotherapy intensity modulated radiation therapy (IMRT) and fixed-field IMRT for nasopharyngeal carcinoma (NPC), as compared with those of conventional beam arrangements. Twelve patients with NPC (T2-4N1-3M0) at Mallinckrodt Institute of Radiology underwent computed tomography simulation. Images were then transferred to a virtual simulation workstation computer for target contouring. Target gross tumor volumes (GTV) were primary nasopharyngeal tumor (GTV(NP)) with a prescription of 70 Gy, grossly enlarged cervical nodes (GTV(LN)) with a prescription of 70 Gy, and the uninvolved cervical lymphatics [designated as the clinical tumor volume (CTV)] with a prescription of 60 Gy. Critical organs, including the parotid gland, spinal cord, brain stem, mandible, and pituitary gland, were also delineated. Conventional beam arrangements were designed following the guidelines of Intergroup (SWOG, RTOG, ECOG) NPC Study 0099 in which the dose was prescribed to the central axis and the target volumes were aimed to receive the prescribed dose +/- 10%. Similar dosimetric criteria were used to assess the target volume coverage capability of IMRT. Serial tomotherapy IMRT was planned using a 0.86-cm wide multivane collimator, while a dynamic multileaf collimator system with five equally spaced fixed gantry angles was designated for fixed-beam IMRT. The fractional volume of each critical organ that received a certain predefined threshold dose was obtained from dose-volume histograms of each organ in either the three-dimensional or IMRT treatment planning computer systems. Statistical analysis (paired t-test) was used to examine statistical significance. We found that serial tomotherapy achieved similar target volume coverage as conventional techniques (97.8 +/- 2.3% vs. 98.9 +/- 1.3%). The static-field IMRT technique (five equally spaced fields) was inferior, with 92.1 +/- 8.6% fractional GTV(NP) receiving 70 Gy +/- 10% dose (P < 0.05). However, GTV(LN) coverage of 70 Gy was significantly better with both IMRT techniques (96.1 +/- 3.2%, 87.7 +/- 10.6%, and 42.2 +/- 21% for tomotherapy, fixed-field IMRT, and conventional therapy, respectively). CTV coverage of 60 Gy was also significantly better with the IMRT techniques. Parotid gland sparing was quantified by evaluating the fractional volume of parotid gland receiving more than 30 Gy; 66.6 +/- 15%, 48.3 +/- 4%, and 93 +/- 10% of the parotid volume received more than 30 Gy using tomotherapy, fixed-field IMRT, and conventional therapy, respectively (P < 0.05). Fixed-field IMRT technique had the best parotid-sparing effect despite less desirable target coverage. The pituitary gland, mandible, spinal cord, and brain stem were also better spared by both IMRT techniques. These encouraging dosimetric results substantiate the theoretical advantage of inverse-planning IMRT in the management of NPC. We showed that target coverage of the primary tumor was maintained and nodal coverage was improved, as compared with conventional beam arrangements. The ability of IMRT to spare the parotid glands is exciting, and a prospective clinical study is currently underway at our institution to address the optimal parotid dose-volume needs to be spared to prevent xerostomia and to improve the quality of life in patients with NPC.