We review here the case histories and results of in vivo and in vitro tests for eight children with congenital selective glucose and galactose malabsorption (GGM) whom our laboratory has followed up since 1971. Clinically, GGM was manifested by intractable, acidic, sugar-containing diarrhea that started during the neonatal period. Diarrhea only abated when glucose and galactose were removed from the diet. The disease was notable for the absence of other symptoms, although mellituria was a common finding. Defective sugar transport was permanent, but sugar tolerance appeared to increase with age. In vitro, intracellular mucosal glucose concentration (C) was significantly below control level in GGM intestinal tissue for concentrations (M) of 10 and 0.1 mM glucose in the medium. C/M for galactose also decreased, while the C/M ratios for alanine and xylose were within the control range. Glucose influxes across the luminal membrane, net glucose transepithelial fluxes, and electrical parameters were all consistent with defective sodium and glucose cotransport at the brush border membrane of jejunal epithelial cells. However, the present results are also consistent with a small residual active transport system observed only at low glucose concentration in the medium. Further observations are needed to establish the role of glucose transport systems in absorption of other monosaccharides, the relationship between kidney and intestinal sodium-glucose cotransport systems, and their genetic control.