The effect of methylprednisolone (MP), Depo-Medrol, on the development of radiologically detectable changes, i.e. thickening and stiffening in rabbit knees following a standard immobilization method, was investigated. The right knees of 34 rabbits were immobilized by a splint and an elastic bandage in extension for five weeks, whereafter the splint was removed. Twelve of the rabbits were given MP in the back muscles once a week during the immobilization period only and eight other rabbits were given diminishing doses during the immobilization period and also during the remobilization period. Marked radiologically detectable changes, stiffening, and thickening developed regularly in the immobilized knees of the rabbits which were not given MP. In the other rabbits MP had a significant preventive effect on the development of all these pathological signs. The degree of the effect of MP was related to the dose and to the administration period. The optimal effect was registered when MP was given initially in large but then gradually diminishing doses during the immobilization and the remobilization periods.