4-Alkylphenols induce Ca2+ release from junctional (terminal cisternae) sarcoplasmic reticulum vesicles, but not from nonjunctional sarcoplasmic reticulum vesicles. The 4-alkylphenol concentration required to induce Ca2+ release decreases about threefold for every methylene carbon increase in the alkyl chain length, indicating that the Ca(2+)-releasing potency of 4-alkylphenols is related to their ability to partition into the membrane. The rate and amount of Ca2+ release induced by relatively low 4-octylphenol concentrations (25 nmol/mg protein) are altered by the sarcoplasmic reticulum Ca2+ channel activators, Ca2+ and ATP, and the Ca2+ channel inhibitors, Mg2+ and ruthenium red. Ca2+ release induced by 250 nmol 4-octylphenol/mg protein is much less influenced by Ca2+ channel activators and inhibitors; however, even at this high 4-octylphenol concentration, Ca2+ release is not induced from nonjunctional sarcoplasmic reticulum vesicles. The data indicate that 4-alkylphenols induce Ca2+ release by activating the sarcoplasmic reticulum Ca2+ channel.