The permeability of isolated frog sartorius muscles to 3-O-methylglucose is increased by low concentrations of insulin, but is relatively insensitive to a variety of other peptides and proteins, many of which have been reported to enhance the uptake and metabolism of glucose by rat hemidiaphragms or adipose tissue in vitro. ACTH, growth hormone, oxytocin, vasopressin and the separated chains of oxidized insulin and of insulin S-sulfonate did not alter the permeability of frog muscles to sugar when tested either alone or together with a submaximal concentration of insulin. These substances were able to retard the degradation of I-131 insulin by frog muscle extracts, but, in contrast to the situation for rat hemidiaphragms, media that had been used for incubation of frog sartorius muscles exhibited only a barely detectable ability to degrade I-131 insulin. The results suggest that some of these peptides may augment the effect of insulin on rat hemidiaphragms by diminishing the rate of degradation of insulin in the medium. Glucagon increased the permeability of frog muscles to sugar, but this effect seemed to be attributable to contamination of the preparation with insulin. Prolactin, TSH and epinephrine augmented permeability to 3-methylglucose when used at concentrations that were higher than those ordinarily found in plasma.