The influence of Ca++, several drugs, and pH on the binding of Ca++ by skeletal muscle microsomes was studied in vitro. A mass-law graphic analysis revealed the presence of three distinct species of Ca+ +-binding sites in the microsomes, and the binding at only one of these sites was antagonized by local anestheth and quinidine. These drugs also decreased the maximum Ca+ +-binding capacity of the microsomes. Caffeine and ouabain exerted no effect on the binding at any of the sites. Procaine was also bound by microsomes, and this binding was antagonized by Ca++, which also decreased the maximum procaine-binding capacity of microsomes. The sites that bind procaine and Ca++ are not identical because the maximum-binding capacities of the interacting sites are distinctly different. The influence of pH on the
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