Above a threshold of 3.0-4.2 mmol/l, D-glucose provoked a transient increase in 32P fractional outflow rate from rat pancreatic islets prelabelled with 32P-orthophosphate. Nutrients which stimulate insulin release in the absence of glucose, alpha-ketoisocaproate and L-leucine, also provoked a phosphate flush. No flush occurred in islets exposed to non-insulinotropic nutrients (L-glutamine and and L-lactate) or non-nutriet secretagogues (arginine, tolbutamide, theophylline). A late increase in 32P fractional outflow rate was observed in Ca2+ deprived islets stimulated with BaCl2 and theophylline. The occurrence of a phosphate flush did not appear to be attributable to changes in insulin release, cyclic AMP content, membrane polarisation, K+ conductance, or reduced pyridine nucleotide content. The 32P response to glucose was slightly decreased in the absence of extracellular Ca2+ or HCO3-, markedly impaired in the absence of K4, and virtually abolished in the presence of menadione (10 mumol/l). It is proposed that the occurrence of a phosphate flush is linked to the metabolism of nutrient secretagogues, possibly via an increase in O2 uptake and the production rate of NAD(P)H and ATP.