INTRODUCTION: Anencephaly is the most severe neural tube defect in human fetuses. There is an increasing need for tissue replacement in chronic diseases and reconstructive surgeries. Fetal tissues have been used as a substitute for native organs. AIM: The aim of this article was to compare the structure and morphology of the corpora cavernosa (CC) and spongiosum (SP) of penises from anencephalic and normal human fetuses. MAIN OUTCOME MEASURES: The main outcome measures of this study were the proposition of a new model for biological studies and tissue transplantation. METHODS: We studied 11 penises from normal human fetuses, aged 14-23 weeks postconception (WPC), and five penises from anencephalic fetuses, aged 18-22 WPC. The organs were removed and processed by routine histological and immunolabeling techniques. Analysis of connective tissue (Cot), smooth muscle (SMC), and elastic fiber (EF) were performed in sections. Data were expressed as area density (Ad) using digital processing and software. Means were statistically compared using the unpaired t-test and linear regression was performed. Statistical significance was considered if P<0.05. RESULTS: The intracavernosal septum was present in all samples. We did not observe differences in the Ad of Cot and SMC in the penises of anencephalic fetuses when compared with normal ones. The simple linear regression suggested that during human development, there is a gradual increase in Cot (R(2)=+0.45) and a decrease of SMC (R(2)=-0.62) in the CC in both groups studied. Elastin was observed only in fetuses from 20th WPC. CONCLUSIONS: There was no difference in the structure of the CC and corpus SP of anencephalic fetuses compared with normal ones. Elastin was documented from 20th WPC, which suggests the maintenance of erectile function. Histochemistry and immunolabeling suggested that penile shaft development is maintained and unaltered in anencephalic fetuses. Further studies should be performed to analyze anencephalic fetuses as a potential tissue-donating group and a model for biological studies.