Mechanically skinned fibre preparations from the extensor digitorum longus muscle of the rat were used to test whether a rise in myoplasmic [NH+4] in the range 2-10 mM interferes with the mechanism of excitation-contraction coupling in fast-twitch mammalian muscle. Under our conditions (pH 7.10, Mg2+ 1 mM, temperature 23 degrees C), [NH+4] up to 10 mM had little effect on the Ca(+)-activated force and on the peak of the t-system depolarization-induced force response. However, the duration of the depolarization-induced force response was decreased significantly at [NH+4] > or = 2 mM. From these data we conclude that the intracellular accumulation of NH+4 is not likely to play a major role in fatigue. Nevertheless, the build up of NH+4 during fatigue, may have a significant inhibitory effect on the force output by decreasing the duration of the t-system depolarization-induced activation of the contractile apparatus.