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To study the distribution of HIV-1 receptors and degree of keratinization in the human penis.Formalin-fixed penises were obtained from nine uncircumcised cadavers. Foreskins were obtained from 21 healthy adult men undergoing elective circumcision for social reasons. Uncircumcised penises were obtained within 24 h of death from eight men. All tissues were stained for keratin and HIV-1 receptors.Penises from nine formalin fixed cadavers aged 64–80 years were obtained from the Department of Anatomy, University of Melbourne. Foreskins were obtained from 21 men aged 18–64 years following circumcision performed at either the Freemason's or Mercy Private Hospitals, Melbourne, Australia. Fresh penile necropsy specimens from eight uncircumcised men aged 23–63 years were obtained from the Victorian Institute of Forensic Medicine, Melbourne. The degree of keratinization was scored, and the distribution of HIV-1 susceptible cells was mapped in the glans penis, penile urethra, urethral meatus, frenulum and foreskin.Cells with HIV-1 receptors were present in all penile epithelia, but Langerhans' cells were most superficial in the inner foreskin and frenulum. The inner foreskin had a significantly thinner keratin layer (1.8 ± 0.1 units), than the outer foreskin (3.3 ± 0.1), or glans penis (3.3 ± 0.2), P < 0.05.Superficial Langerhans' cells on the inner aspect of the foreskin and frenulum are poorly protected by keratin and thus could play an important role in primary male infection. These findings provide a possible anatomical explanation for the epidemiologically observed protective effect of male circumcision.