We have reported that the mouse ventro-lateral hypothalamus releases a humoral factor in vitro which stimulates insulin secretion by isolated islets (Idahl & Martin, 1971). We report here similar studies extended to rats, and attempts to isolate this hypothalamic factor and to demonstrate its presence in blood. Ventro-lateral (VLH) and ventro-medial hypothalami (VMH) of 16 rats were separated and extracted with 3 ml Gey & Gey (1936) buffer at 37 °C for 30 min. Aliquots (0·4 ml) of the extract were tested for stimulatory capacity by incubation (20 min at 37 °C) with five islets of Langerhans. The incubation medium contained glucose (3·3 mmol/l and albumin (1 mg/ml), in a final volume of 0·5 ml Gey & Gey buffer. The amount of insulin released into the medium was compared with the amount released by the same islets during a preliminary 20-min incubation in a medium without the extract (baseline). Insulin