The effects of sugars such as glucose or mannose in promoting release of insulin from beta cells appears to be paralleled by a simultaneous increase in insulin synthesis (Parry & Taylor, 1966). It has been argued that such effects are physiologically important in that they prevent an undue depletion of β cell reserves of insulin under conditions of maximal stimulation by sugars. Whether the secretion of insulin induced by drugs like tolbutamide is also accompanied by a simultaneous enhancement of insulin synthesis is not known. Work on animals in vivo suggests that tolbutamide may very rapidly deplete the pancreas of insulin (Root, 1957). The experiments to be reported suggest that tolbutamide is without effects on the incorporation of amino acids into insulin. Effects of tolbutamide were tested on incorporation into rabbit insulin in vitro, by methods described in detail elsewhere (Taylor, Gardner, Parry & Jones, 1965; Mallory, Smith & Taylor,