A new optimization model is described and its clinical usefulness is demonstrated. The optimization technique was developed to allow computer optimization of 3-dimensional radiation therapy plans with biological models of tumor and normal tissue response to radiation as well as with scores based on physical dose. The emphasis was placed on the optimization model, which should describe, as closely as possible, the goal of the radiation treatment, which is eradication of the tumor while sparing normal tissues. Since the statement of the goals may vary from case to case, a technique that allows a variety of objective functions and types of constraints was developed. The optimization algorithm is capable of handling nonlinear and even discrete score (objective) functions and constraints and effectively explores the vast space of feasible solutions in a relatively short time (minutes of MicroVax 3200 CPU time). An example of computer optimization of radiation therapy of a chordoma of the sphenoid bone using x-ray and proton beams is shown and compared with the best plans achieved by an experienced planner. Directions for future development of the algorithm, allowing optimization of beam orientation, are presented.