The long terra effects of glucose on the rate of (pro) insulin biosynthesis and the amount of preproinsulin mRNA in rat islets maintained in tissue culture were investigated. The rate of (pro)insulin synthesis was 35 times greater in islets cultured for 6 days in 8 mM glucose than it was in islets cultured in 4 mM glucose. The preproinsulin mRNA content at this time was 2 fold greater in islets incubated with 8 mM glucose compared to 4 mM glucose. The rate of (pro)insulin synthesis and the preproinsulin mRNA content of islets cultured at 8 mM glucose were maximal since no further significant increases were observed in islets cultured at 16 mM glucose for 6 days. These results indicate that the long term effects of glucose on the rate of (pro)insulin synthesis in rat islets of Langerhans is mediated both by transcriptional and translational events and that translational events exert the major controlling influence.