At least four genes encode the human alkaline phosphatases (ALPs). The genes encoding three of these proteins (intestinal, placental, and placental-like ALPs), are linked on the long arm of chromosome 2, while the fourth gene (encoding liver/bone/kidney ALP) is located on chromosome 1. One of the linked genes, intestinal alkaline phosphatase, has been isolated on two overlapping phage clones and sequenced in its entirety. The gene is composed of 11 exons interrupted by 10 introns. Introns in intestinal, placental, and liver/bone/kidney ALPs occur at analogous positions (see accompanying articles), confirming that these genes arose from a single ancestral ALP gene. Multiple intestinal ALP mRNA species can be detected in RNA isolated from adult and fetal intestine and from cell line RNAs. In cell line RNA, the various species are the result of differential use of at least three of the four polyadenylation signals present in the intestinal ALP gene. A 125-base pair fragment located 5' to the first exon can function as a promoter in mammalian cells. This region contains two putative transcription signals, a TATA-like sequence and a consensus binding site for the transcription factor Sp1.