In bitches in anestrus, artificial endometrial sex cycles were induced. Estrus was induced by 17 beta-estradiol benzoate administration; matched untreated and vehicle-treated controls were studied. Early metadiestrus (6th day after appearance of metestrum cells in vaginal smears) was induced by the sequential administration of 17 beta-estradiol benzoate and progesterone: matched studies with only one hormone or vehicles were also carried out. In different groups of animals, blood sugar (BS), serum immunoreactive insulin (IRI) and serum free fatty acids (FFA) in the basal conditions and during glucose and insulin tests were studied. Insulin was immunocytolocalized in sections of pancreas from a part of these animals. Size and insulin content in Langerhans islets were measured by morphometric and cytospectrophotometric computerized analysis. Extra-pancreatic factors--space of distribution, t1/2 in blood stream--regulating serum IRI and BS levels were calculated. The hypoglycemic effect of insulin was enhanced by estrogenization, together with insulin accumulation in Langerhans islets. Progesterone treatment caused mild insulin resistance together with depletion of pancreatic insulin stores in the long run. Glucose tolerance of progesterone-injected bitches was improved after estrogen priming with greater space of distribution of glucose. Furthermore, a high basal serum FFA levels in bitches receiving the hormone sequence was observed. We may therefore conclude that the metabolic and endocrine changes induced in bitches by artificial sex cycles converge towards excellent BS homeostasis leads to the replenishing of pancreatic insulin stores, so that estrogen-progesterone administration in sequence appears to be, in this experimental condition, non-diabetogenic.