The efficacy of a resistance exercise paradigm, using a gravity-independent flywheel principle, was examined in four men subjected to 110 days of confinement (simulation of flight of international crew on space station; SFINCSS-99). Subjects performed six upper- and lower-body exercises (calf raise, squat, back extension, seated row, lateral shoulder raise, biceps curl) 2-3 times weekly during the confinement. The exercise regimen consisted of four sets of ten repetitions of each exercise at estimated 80-100% of maximal effort. Work was measured and recorded in each exercise session. Maximal voluntary isometric force in the calf press, squat and back extension, was assessed at three different joint angles before and after confinement. Overall, the training load (work) increased in all subjects (range 16-108%) over the course of the intervention. Maximal voluntary isometric force was unchanged following confinement. Although the perceived level of strain and comfort varied between exercises and among individuals, the results of the present study suggest this resistance exercise regimen is effective in maintaining or even increasing performance and maximal force output during long-term confinement. These findings should be considered in the design of resistance exercise hardware and prescriptions to be employed on the International Space Station.