The overall objective of this program is to evaluate the efficacy, potential benefit, and role of negative pi mesons (pions) in radiotherapy for the management of all types and stages of solid tumors not well managed by current treatment methods or combinations thereof. Phase I-II clinical investigations provide data and experience on the usefulness of pions in treating tumors at several sites, leading to Phase III randomized trials in which pion treatment is compared directly to conventional radiotherapeutic treatment for particular sites. Physics studies develop the pion treatment beam hardware and software, provide basic understanding of pion-beam characteristics, and evolve techniques for measuring dose distribution and volume. Biology studies provide a more definitive understanding of the biologic actions and relative biologic effectiveness of pions, as compared to x-rays, in vivo and in vitro. The linear accelerator at Los Alamos continues to be the only facility in the world that can provide a pion flux adequate for treating clinically relevant volumes. Continued improvement in beam output and treatment technique and the institution of Phase III trials for new sites, should permit a meaningful comparison of the relative effectiveness of pion treatment versus conventional photon treatment.