The effects of ryanodine and iodoacetamide were examined on bundles isolated from diaphragm muscles of normal and dystrophic mice (C57 BL 6J strains). At 22°C, the addition of ryanodine or iodoacetamide for external concentrations higher than 10-7 M and 5 × 10-4 M respectively produced an irreversible increase in the resting tension after a period of 20-40 min. For both drugs the latent period was reduced if K-contractures were generated simultaneously. However, in the presence of ryanodine the phasic K-contracture was followed by a slow and transient increase in tension. The peak value of this second phase related to the amplitude of the 110 mM K-contracture was always smaller in dystrophic than in normal diaphragm muscle. Using lower concentrations, the effects of the two drugs were examined on the repriming of 110 mM [K]0-contractures. Following application of iodoacetamide (5-10-6 M to 10-4 M) the recovery time was increased to the same extent in both types of muscle. By contrast, for a given amount of ryanodine, the rate of repriming was more affected in normal than in dystrophic muscles. It is proposed that ryanodine acts at a specific site of the terminal cisternae from the sarcoplasmic reticulum (SR) where dystrophy induces pathological modifications.