Destruction of the ventro-medial region of the hypothalamus results in hyperinsulinism (Hales & Kennedy, 1964; Frohman, Bernadis, Schnatz & Burek, 1969) and enlargement of the islets of Langerhans (Coleman & Hummel, 1970; Han, Yu & Chow, 1970), demonstrable a few hours after making the lesion (Martin & Bouman, 1971). These changes are progressive and independent of the ensuing hyperphagia (Han et al. 1970; Martin & Bouman, 1971). Whether this direct hypothalamic effect was mediated by the autonomic nervous system or by a humoral factor was not determined. We investigated the latter possibility by exposing isolated islets of Langerhans, dissected from mouse pancreas (Hellman, 1970), to the effect of pieces of hypothalamus from either the medial or lateral region. The islets were located in a 10 μl chamber and perfused with Krebs-Ringer bicarbonate buffer supplemented with either 5·6 or 16·7 mm-glucose (Idahl, 1970). An additional chamber containing the hypothalamic tissue - or