Reactive oxygen and nitrogen species (ROS/RNS) are important for skeletal muscle function under both physiological and pathological conditions. ROS/RNS induce long-term and acute effects and the latter are the focus of the present review. Upon repeated muscle activation both oxygen and nitrogen free radicals likely increase and acutely affect contractile function. Although fluorescent indicators often detect only modest increases in ROS during repeated activation, there are numerous studies showing that manipulations of ROS can affect muscle fatigue development and recovery. Exposure of intact muscle fibres to the oxidant hydrogen peroxide (H(2)O(2)) affects mainly the myofibrillar function, where an initial increase in Ca(2+) sensitivity is followed by a decrease. Experiments on skinned fibres show that these effects can be attributed to H(2)O(2) interacting with glutathione and myoglobin, respectively. The primary RNS, nitric oxide (NO()), may also acutely affect myofibrillar function and decrease the Ca(2+) sensitivity. H(2)O(2) can oxidize the sarcoplasmic reticulum Ca(2+) release channels. This oxidation has a large stimulatory effect on Ca(2+)-induced Ca(2+) release of isolated channels, whereas it has little or no effect on the physiological, action potential-induced Ca(2+) release in skinned and intact muscle fibres. Thus, acute effects of ROS/RNS on muscle function are likely to be mediated by changes in myofibrillar Ca(2+) sensitivity, which can contribute to the development of muscle fatigue or alternatively help counter it.