In order to avoid viral contamination or reduce the incidence it is helpful to know the source of the contamination. Viruses can be introduced by a limited number of different routes and knowing this provides the possibility to avoid infection. The identified routes of infection are: (i) the cells used to produce the production cells are already contaminated by exogenous virus because the cells were already contaminated at source, e.g., the donor animal from which the cells were explanted (see 'Contamination via the cell source'), the pre-culture (in vitro), or the in vivo passage in an animal led to the virus contamination (see 'Passages via virus infected animals'). (ii) Endogenous viruses, such as retroviruses are a particular concern. Several cell lines of biotechnological importance, such as murine hybridomas or Chinese Hamster Ovary (CHO) cells, contain endogenous retroviruses and can produce retroviral particles during production. In the case of murine retroviruses these can be capable of replication, as observed with hybridoma cells, or which are incapable of replication, as in the case of CHO-cells (see 'Cell lines of biotechnological interest-endogenous retroviruses and other cell associated/latent viruses'). (iii) The cell cultures can be contaminated by viruses which were present in the animal derived materials used in the manipulation or for the growth of the cells. These types of materials include serum or trypsin (see 'Use of contaminated raw materials'). Animal derived raw materials are of particular concern as many different animal viruses can potentially be present originating from the use of infected source animals. Non-animal derived raw materials can also be contaminated by viruses due to contact with virus shed from animals or man from production until its eventual use in the medium of which they are a component. (iv) Finally, errors made by the operator can also result in viral contamination of animal cells (see 'Handling errors of the operator').