It has been hypothesized that poor semen quality, testis cancer, undescended testis and hypospadias are symptoms of one underlying entity, the so-called testicular dysgenesis syndrome (TDS). TDS was suggested to be a result of disruption of embryonal programming and gonadal development during foetal life and as aetiological factor, an impact of adverse environmental factors such as hormone disrupters, probably acting upon a susceptible genetic background, was suggested. Extensive studies considering the risk of TDS-related diseases in Denmark compared with Finland, showed higher sperm counts and lower risk of cryptorchidism and testicular cancer among Finns. However, when comparing these two populations, the question arises, to which degree this difference might be due to discrepancy in genetic background. A more obvious example of the impact of genetic factors on the risk of TDS concerns Afro-Americans having significantly lower incidence of testicular cancer when compared with Caucasians living in the USA. A yet unexplored scenario is a possible interaction between genetic and environmental/lifestyle-related factors, certain genotypes making individuals more susceptible to adverse exogenous exposures. Studying such interactions has biological, epidemiological and public health-related implications. It will help us to understand the background for the defects in male reproductive organs, facilitate proper design of epidemiological studies and add to identifying individuals susceptible to certain environmental and lifestyle-related hazards. Such ‘susceptibility genes’ need to be identified, those involved in the synthesis, action and metabolism of sex steroids being strong candidates.