Three opioids, viz. methadone, morphine and meperidine, were tested separately for their effects on the rate of 45Ca++ efflux from frog toe muscles. The experimental procedures were designed to provide reliable measurements of the displacement of 45Ca++ from surface binding sites using the thin and light toe muscle. La (2 mM) was used to test the ability of the experimental procedure to detect the displacement of calcium bound superficially to the muscle fiber membrane. La not only enhances the rate of efflux of 45Ca++ from surface membrane superficial stores but also inhibits the efflux of intracellular calcium. Of the opioids tested, only methadone (10(-4) or 10(-3) M) caused a slight but significant increase in the rate of 45Ca++ efflux from the surface bound (i.e., the La -displaceable) store of calcium of the muscle. The "calcium-displacement" effect of methadone was much weaker than that seen with La . Morphine (10(-4) or 10(-3) M) or meperidine (10(-4) or 10(-3) M) did not show any such effect on the bound 45Ca++ desaturation rate even under experimental conditions modified to enable the detection of the displacement of even small amounts of 45Ca++ from superficial binding sites on the muscles.