Lactase is an enterocyte brush-border membrane beta-glycosidase that splits lactose, the sugar of milk. In mammals, including many human populations, intestinal lactase activity is very high in the suckling and declines to low levels after weaning. There are two human adult lactase phenotypes, one in which high lactase activity persists and another in which it declines. Two alleles have been postulated to explain these different phenotypes. In the present study lactase mRNA levels have been investigated in the small intestine (a) of rabbits and rats, at different ages, considered as models for mammals, and (b) of human adults with the two lactase phenotypes. In rabbits and rats, high levels of lactase mRNA are present up to the weaning period, a time at which a consistent decrease of this mRNA is found, a decrease that parallels that of lactase activity. It is surprising that after this period adult animals of both species express again high levels of lactase mRNA, whereas lactase activity remains at very low levels. Our results suggest that in the adult rabbits and rats the main control of lactase gene expression is likely to be at a posttranscriptional level. Similarly, in man no clear difference was found at the RNA level between adults with hypolactasia and adults with persistent high lactase activity, a result that also indicates a posttranscriptional control of lactase expression.