Caffeine sensitivity was studied in chemically skinned muscle fibers from vastus lateralis muscle obtained by biopsy during reconstructive knee surgery from 15 otherwise healthy young individuals. Muscle fiber type was determined by contracture occurring in strontium (slow-oxidative, type I fiber) or calcium (both type I and type II, fast glycolytic fiber) solutions and in several fibers after contracture testing by ATPase enzyme histochemistry. Caffeine sensitivity (mean ± SD), defined as the threshold concentration inducing more than 10% of the maximal tension obtained with a calcium 3 × 10−5mM solution was 2.7 ± 1.3 mM in 37 type I fibers, whereas it was 6.9 ± 2.4 mM in 61 type II fibers. A pairedttest showed a significantly increased sensitivity to caffeine in type I fibers (P< 0.001) in 13 individuals in whom the two fiber types were identified. The mean (±SD) difference between type I and type II fibers was 4.1 ± 1.9 mM. Type I fibers contracted with greater tension in response to the increasing concentration of caffeine than did type II fibers (P< 0.05). These skinned fiber studies showed significantly different caffeine sensitivities between human type I and type II muscle fibers, as previously shown in animal muscles. The findings that human type I muscle fibers have higher caffeine sensitivity than type II muscle fibers should be helpful for the interpretation of thein vitrocontracture test done in muscle strips containing type I and type II fibers in varying proportions.