Human placental chorionic somatomammotropin (hCS-A or hCS-B) and pituitary growth hormone (hGH-N) are related by structure and function. The hCS-A gene is expressed in rat pituitary tumour (GC) cells after gene transfer. Deletion of hCS-A 5'-flanking DNA reveals repressor activity upstream of nucleotide -132, and a region essential for expression in GC cells between nucleotides -94 and -61. The sequences in this region differ from the equivalent hGH-N gene DNA by one nucleotide, and include the binding site (-92 to -65) for a pituitary-specific factor (GHF-1), required for hGH-N expression in GC cells. Exchange of hGH-N with hCS-A gene DNA in this region maintains expression in GC cells. By contrast, modification of these sequences blocks expression. These data indicate that proximal promoter sequences, equivalent to those bound by GHF-1 on the hGH-N gene, are required for hCS-A expression in GC cells.