Kinetic aspects of immunoreactive insulin (IRI) release in response to glucose 0.5 g/ kg ip or iv have been studied in obob and DBM mutant mice, randomly bred Swiss white mice rendered obese by gold thioglucose (GTG), and spiny mice (Acomys cahirinus). Intraperitoneal tests showed that obob and GTG obese mice had elevated basal plasma IRI levels and an excessive response to stimulation. Absolute plasma IRI levels were approximately three times higher in obob than in GTG obese mice. By contrast, Acomys cahirinus had neither elevated basal IRI levels nor an excessive response when compared to control CS7B1/6 or lean Swiss white mice. Intravenous glucose administration resulted in a rapid IRI release in obob and GTG obese mice, peak plasma levels being seen at 1 min. DBM mice with overnight fasted plasma glucose levels of less than ISO mg/100 ml similarly showed elevated basal IRI levels and a rapid initial release. DBM animals with higher fasted plasma glucose levels however had an impaired secretory response to iv glucose in the presence of markedly elevated basal plasma IRI. These observations suggest that, in rodents, hyperinsulinaemia is not a necessary concomitant of overt obesity and that a defective initial phase of IRI release is not necessarily a primary abnormality in those animals subsequently developing carbohydrate intolerance. (Endocrinology92: 257, 1972)