The exact cause and nature of various ocular diseases are still unknown. In accordance with the progress of modern medical science, technology for research investigations has greatly developed and a variety of new results have recently been produced. However, they were mostly about exogenous factors such as bacteria or parasites. On the other hand, molecular biology has markedly progressed in the second half of the 20th century and has been applied to medical science. As for the exogenous factors, molecular techniques have been introduced to the diagnosis of infectious diseases, and their diagnosis has become much easier and much more exact than before. Similarly, in the field of immunogenetics, molecular genetics has greatly developed, and disease susceptibility or disease resistance has been investigated at the DNA or molecular level. Regarding the exogenous disease mechanisms, most infectious diseases occur when the microorganisms are transmitted to some individuals. In this case, endogenous factors play almost no or very little role. Adenovirus keratoconjunctivitis is one example. Human adenovirus (HAdV) is a DNA virus. Although HAdVs are classified into 51 different serotypes, only 7 of them such as HAdV-3, -4, -7, -8, -11, -19, and -37 usually develop acute keratoconjunctivitis. The genome of HAdV develops constant mutation, and new genome types often cause epidemics of nosocomial infections. Recent studies showed that most of the keratoconjunctivitis cases are caused by HAdV-37 in Japan. With regard to the endogenous disease mechanisms, only 30 years have passed since the recent molecular genetic studies on disease susceptibility started. Before that, genetic disease mechanisms were studied only in hereditary diseases such as color vision defects, which follow the modes of Mendelian inheritance. Therefore, the presence of disease susceptibility was not clearly understood in the so-called nonhereditary diseases. However, after our initial findings of the close association between Behçet's disease and HL-A 5 (later HLA-B 5 or HLA-B 51) in 1973, there were many reports on the presence of genetic predisposition to certain non-hereditary diseases. One example is Vogt-Koyanagi-Harada's (VKH) disease which has a close association with HLA-DRB 1*0405 in Japanese patients, as also was the case with sympathetic ophthalmia. These studies indicate that Behçet's disease may be called "a disease of the Yayoi people" and Vogt-Koyanagi-Harada's disease as "a disease of the Jomon people" when analyze the associated genetic factors. On the other hand, the human genome project has been successfully completed and it is now possible for us to investigate any genetic factor associated with certain diseases either on 22 pairs of autosomal chromosomes or on one pair of sex chromosomes. Our collaborative team has adopted the microsatellite methods utilizing the pooled DNA PCR method, and started investigation of any genetic association with ocular diseases, in addition to the HLA system on the short arm of autosomal chromosome 6. In the first screening of 100 DNA samples of Behçet's disease patients, for example, 9 % of microsatellite markers on the autosomal chromosomes 1, 6, 17, and 19 showed significant positive association. The same studies are now in progress by our collaborative team on inflammatory diseases such as sarcoidosis, and on noninflammatory conditions like hypertension or high myopia. These results suggest that exogenous environmental factors such as infections which may trigger the occurrence of the disease or conditions, and endogenous genetic factors which may predispose someone to contracting a disease, are both significantly associated with various ocular diseases, and construct intricate disease mechanisms. Therefore, in future studies of diagnosis, treatment, and prevention of various ocular diseases, both exogenous factors and endogenous factors have to be carefully analyzed and investigated.