PURPOSE: The alpha/beta ratio for prostate cancer is postulated to be between 1 and 3, giving rise to the hypothesis that there may be a therapeutic advantage to hypofractionation. The dosimetry and acute toxicity are described in the first 100 men enrolled in a randomized trial. PATIENTS AND METHODS: The trial compares 76 Gy in 38 fractions (Arm I) to 70.2 Gy in 26 fractions (Arm II) using intensity modulated radiotherapy. The planning target volume (PTV) margins in Arms I and II were 5 mm and 3 mm posteriorly and 8 mm and 7 mm in all other dimensions. The PTV D95% was at least the prescription dose. RESULTS: The mean PTV doses for Arms I and II were 81.1 and 73.8 Gy. There were no differences in overall maximum acute gastrointestinal (GI) or genitourinary (GU) toxicity acutely. However, there was a slight but significant increase in Arm II GI toxicity during Weeks 2, 3, and 4. In multivariate analyses, only the combined rectal DVH parameter of V65 Gy/V50 Gy was significant for GI toxicity and the bladder volume for GU toxicity. CONCLUSION: Hypofractionation at 2.7 Gy per fraction to 70.2 Gy was well tolerated acutely using the planning conditions described.