Lactose and glucose-galactose tolerance tests and dietary histories were obtained in 22 members of four families (two Negro and two white families). On the basis of flat lactose tolerance tests, 16 of the 22 individuals had a diagnosis of an isolated lactase deficiency which was further confirmed in two individuals by assays of intestinal disaccharidase activity. Lactose intolerance was present in more than one generation of each family; there was no sex predilection and a history of milk intolerance was more common in the older individuals with the defect. These data support a genetic factor in the etiology of an isolated lactase deficiency with late onset of symptoms.