The effects of delta sleep-inducing peptide (DSIP) on pituitary cell differentiation was studied using an in vitro method and immunocytochemical techniques. Pituitary primordia were explanted from 11-day-old rat fetuses and cultured in a synthetic medium enriched with either DSIP at several concentrations, GnRH (10–9M) or TRH (10–9M). Expression of different pituitary phenotypes was quantified as the percentage of immunoreactive area per section of cultured primordia. Addition of DSIP during the first day of culture induced differentiation of LH and TSH cells only. The effect was dose-dependent. DSIP was less potent than GnRH and as potent as TRH in inducing LH and TSH differentiation. DSIP also induced lactotrope differentiation, but this effect may not be direct. DSIP had no effect on somatotrope and corticotrope differentiation. These results obtained in vitro suggest that DSIP exerts a direct action on the differentiation of several pituitary precursor ce