The effects of mannoheptulose and DL-glyceraldehyde on glucose-induced insulin release and cycli AMP levels in islets isolated from rat pancreas were investigated. Mannoheptulose inhibition on glucose-induced insulin release was observed after only 5-min incubation period, indicating an inhibitory effect on the early phase of insulin release. This inhibition on insulin release was accompanied with the simultaneous depression of cyclic AMP levels in islets. By the addition of DL-glyceraldehyde to the medium in which glucose and mannoheptulose were present, the depressed cyclic AMP levels in islets were recovered to the control level completely but the restoration of insulin release in the early phase was not complete. In the absence of glucose, DL-glyceraldehyde did not demonstrate a significant increase of insulin release during 5 min incubation, though a marked stimulation was observed after 30-min incubation. Cyclic AMP levels in islets were not affected by DL-glyceraldehyde. When DL-glyceraldehyde was added to the medium with glucose, significant inhibition of glucos-induced insulin release in its early phase was observed without the reduction of cyclic AMP levels in islets. From these findings, the following possibilities are suggested and discussed. 1. Maintenance of the cyclic AMP levels in islets is a necessary but insufficient condition for glucose-induced insulin release particularly for its early phase. 2. Glucose-induced insulin release seems to depend on both the binding of glucose with glucoreceptor and the supply of some metabolites. Mannoheptulose inhibits both mechanisms. DL-glyceraldehyde may supply metabolites but competitively inhibit the binding of glucose to the glucoreceptor.