1) Most humans, like other mammals, gradually lose the intestinal enzyme lactase after infancy and with it the ability to digest lactose, the principle sugar in milk. At some point in prehistory, a genetic mutation occurred and lactase activity persisted in a majority of the adult population of Northern and Central Europe. 2) Persistence of intestinal lactase, the uncommon trait worldwide, is inherited as a highly penetrant autosomal-dominant characteristic. Both types of progeny are almost equally common when one parent is a lactose maldigester and the other a lactose digester. 3) The incidence of lactose maldigestion is usually determined in adults by the administration in the fasting state of a 50-g dose of lactose in water, the equivalent of that in 1 L of milk. Measurement is made of either the subsequent rise in blood glucose or the appearance of additional hydrogen in the breath. It is also sometimes identified by measuring lactase activity directly in a biopsy sample from the jejunum. For children the test dose is reduced according to weight. Depending on the severity of the lactase deficiency and other factors, the test dose may result in abdominal distention, pain, and diarrhea. 4) The frequency of lactose maldigestion varies widely among populations but is high in nearly all but those of European origin. In North American adults lactose maldigestion is found in approximately 79% of Native Americans, 75% of blacks, 51% of Hispanics, and 21% of Caucasians. In Africa, Asia, and Latin America prevalence rates range from 15-100% depending on the population studied. 5) Whenever the lactose ingested exceeds the capacity of the intestinal lactase to split it into the simple sugars glucose and galactose, which are absorbed directly, it passes undigested to the large intestine. There it is fermented by the colonic flora, with short-chain fatty acids and hydrogen gas as major products. The gas produced can cause abdominal distention and pain and diarrhea may also result from the fermentation products. 6) Among individuals with incomplete lactose digestion, there is considerable variation in awareness of lactose intolerance and in the quantity of lactose that can be ingested without symptoms. A positive standard lactose test is not a reliable predictor of the ability of an individual to consume moderate amounts of milk and milk products without symptoms. In usual situations the quantity of lactose ingested at any one time is much less than in the lactose-tolerance test.(ABSTRACT TRUNCATED AT 400 WORDS)