Muscle fatigued by metabolically demanding exercise typically shows two features, a loss of isometric force and a slowing of contractile properties. Single fibre studies measuring intracellular calcium have shown that loss of force largely coincides with a reduction in calcium release together with a reduced calcium sensitivity (see Allen & Westerblad, 2001). Accumulation of inorganic phosphate may be the cause of the reduced calcium release but might itself shift the equilibrium between low and high force cross bridge states, inhibiting the Pi release step. In single fibres this may account for the small initial drop in force but is unlikely to make a significant contribution in human muscle where, even at rest, levels of Pi (~8mM; Jones et al., 2009) are relatively high while force appears to be most sensitive to Pi in the range of 1-10mM. Slow relaxation of fatigued muscle could be due to a slow removal of activating calcium or to a change in cross bridge kinetics. There are two lines of evidence to suggest that it is predominantly the latter. Measurements of calcium in single fibres show no major changes in calcium handling with fatigue and slow relaxation (Westerblad & Allen, 1993). There is, however, clear evidence that cross bridge kinetics change with fatigue since there is a reduction in the maximum velocity of unloaded shortening (Vmax) and increased curvature of the force-velocity relationship (Jones et al., 2006). The combined effect of these two changes and the loss of isometric force, is a major reduction in power most evident as a slowing of running speed towards the end of a 400m race. The most obvious explanation for the slowing is that the rate of cross bridge detachment is reduced but evidence suggests that, in fact, it is the rate of attachment that changes. Kinetic considerations based on the Huxley (1957) model indicate that the change in curvature is mainly due to a decrease in the sum of the rate constants f, for attachment, and g1 for detachment and since f is probably greater than g1, the only way of effecting a marked drop in (f + g1) is for f to decrease. That it is f rather than g1 which changes is supported by the fact that economy (ATP cost divided by force) during sustained isometric contractions remained constant. Economy is proportional to g1 and thus, by inference, g1 remains constant during a fatiguing contraction (Jones et al., 2006). Slowing is a feature of muscle that is metabolically depleted but there are poor correlations between slowing and changes in H+, ATP, Pi and ADP and this lack of correspondence suggests other explanations might be usefully examined. Although cross bridge kinetics and rate of shortening are generally thought to be independent of the activating calcium, this may not be the case. The sum (f + g1) is equivalent to ktr, the rate at which tension redevelops following rapid shortening and restretch (Brenner, 1988) and is sensitive to the activating calcium with f decreasing at low calcium concentrations. Likewise, the velocity of shortening is also affected by calcium concentrations (Moss, 1986). In the Huxley model Vmax is determined by the rate constant g2 and curvature by the ratio (f + g1)/g2. If both f and g2 are affected by calcium then it is possible that the slowing of Vmax and the decrease in curvature could both be explained by the decline in activating calcium that occurs with fatigue. It would be a remarkable coincidence if calcium affected two separate rate constants, f and g2, but if low calcium slows the transition from low to high force cross bridge states this would be apparent as a reduced f while the increased proportion of attached low force cross bridges would slow shortening velocity and be apparent as a reduction in g2. Thus it is possible that a reduction of intracellular calcium as a result of some metabolic event could be responsible for all three of the characteristic features of fatigued muscle, reduced force, slowing of Vmax and change in curvature. The fly in the ointment is that we have found reducing the activating calcium with skinned fibres at 15oC reduced both (f + g1) and g2, but the reduction in g2 was proportionately greater than (f + g1) so that curvature decreased rather than increasing, as seen with fatigued human muscle. However, this could be a temperature effect if various stages in the cross bridge cycle have different temperature coefficients, and it is reported that muscle fatigue at low temperature decreases curvature (De Ruiter & De Haan, 2000) as opposed to increasing it at higher temperatures. The role of calcium in modulating speed and power, as well as force, during fatiguing contractions deserves further examination.