Anencephalic fetuses provide a model of pituitary development in the absence of the hypothalamus. We studied pituitaries of 10 anencephalic fetuses at various stages of gestation using formalin-fixed paraffin-embedded tissue with immunocytochemistry for known adenohypophysial hormones, the transcription factors Pit-1 and SF-1, cytokeratins and S-100 protein. Ten age- and sex-matched fetuses with no endocrine abnormality were controls. At 17-18 weeks of gestation, pituitaries of 4 anencephalics had no posterior lobe; the number and size of cells containing adenohypophysial hormones and the transcription factors were indistinguishable from controls, however, juxtanuclear cytokeratin-positive fibrous bodies were inconspicuous in anencephalics and were prominent in the adenohypophyses of controls. At 26-28 weeks of gestation, there was a marked reduction in number and staining intensity of cells containing SF-1, α-subunit of glycoprotein hormones and both gonadotropin β-subunits in the adenohypophyses of 2 anencephalics. After 32 weeks, corticotropes were reduced in number and size, and gonadotropes were almost entirely absent; in contrast, somatotropes, lactotropes and thyrotropes were numerous. S-100 protein immunoreactivity was increased in anencephalic pituitaries after 32 weeks, when it was found in numerous cells that did not have the usual morphology of folliculo-stellate cells.