1. Humans have three kallikrein genes: hGK-1, hRKALL (kinin-generating) and a gene encoding prostate specific antigen (PSA). 2. Using a gene-specific oligonucleotide, expression of hGK-1 was demonstrated in human prostate, but not in 10 other tissues examined. 3. The similarity in tissue specificity of expression of hGK-1 with that of the PSA gene led to an examination of putative regulatory DNA. Marked identity of greater than 90% was seen (compared with 80% for hRKALL), thus supporting a role for the operation of similar tissue-specific mechanisms for the control of hGK-1 and the PSA gene. 4. Unique structural features were observed in the protein encoded by hGK-1 suggestive of a capacity for interaction with substrate residues larger than those in kininogen. In particular it is predicted that a glycine at 186 would twist the polypeptide backbone in this crucial, highly conserved active site region and so profoundly influence interaction with substrate.