Hereditary dwarfism was first recognized in inhabitants of the island of Krk in the Adriatic in 1864. Since then 24 related dwarfs have been recorded. Their pedigrees and heights are presented. Ten of these patients live in the villages Bascanska Draga and Jurandvor. Six have been studied by the authors. Clinical examination revealed dwarfism, obesity, dry wrinkled skin, and lack of sexual development. Hormonal investigations showed the absence of growth hormone (GH) unresponsive to growth hormone releasing hormone (GHRH), absence of luteinizing hormone (LH) and follicle stimulating hormone (FSH) unresponsive to gonadotropin releasing hormone (GnRH), and absence of thyrotropin stimulating hormone (TSH) unresponsive to TRH. Basal serum prolactin (PRL) was low but secretion of ACTH was normal as evidenced by normal Cortisol levels. Hypopituitarism in this isolate was not associated with a shortened life span or an increased incidence of diabetes. PROP-1 is a pituitary specific transcription factor that is required for the embryologic development of the pituitary cell types that ultimately produce GH, PRL, TSH and FSH/LH postnatally. Examination of genomic DNA from two of the patients revealed homozygosity for a one bp deletion in codon 50 of exon 2 of PROP-1. This mutation introduces a frame shift and