Since 1982, 49 patients with locally advanced carcinoma of the prostate have been treated with pion radiotherapy in tolerance and tumor response studies. The relative biological effectiveness (RBE) was confirmed as 1.5 for both acute and late effects, a figure expected on the basis of animal and human studies. The radiation dose has been safely escalated to tolerance, which is estimated to be 37.5 Gy pi in 15 fractions (volume less than 500 cc), and 36 Gy pi in 15 fractions (volume 500-800 cc). Severe acute toxicity occurred in 6% and severe chronic toxicity in 4%, figures comparable to those seen with conventional radiotherapy. The equivalent photon doses are approximately 78 Gy in 39 fractions and 73 Gy in 36 fractions, respectively. That this high dose can be delivered with no increase in toxicity is a reflection of smaller volume radiotherapy achieved by exploiting the dose distribution and biological characteristics of pions. Local response rates of 94% are reported. A Phase III study is now under way.