In 1986 we reported that transgenic plants which accumulate the coat protein of tobacco mosaic virus (TMV) are protected from infection by TMV, and by closely related tobamoviruses. The phenomenon is referred to as coat–protein–mediated resistance (CP–MR), and bears certain similarities to cross protection, a phenomenon described by plant pathologists early in this century. Our studies of CP–MR against TMV have demonstrated that transgenically expressed CP interferes with disassembly of TMV particles in the inoculated transgenic cell. However, there is little resistance to local, cell–to–cell spread of infection. CP–MR involves interaction between the transgenic CP and the CP of the challenge virus, and resistance to TMV is greater than to tobamoviruses that have CP genes more distantly related to the transgene. Using the known coordinates of the three–dimensional structure of TMV we developed mutant forms of CP that have stronger inter–subunit interactions, and confer increased levels of CP–MR compared with wild–type CP. Similarly, it is predicted that understanding the cellular and structural basis of CP–MR will lead to the development of variant CP transgenes that each can confer high levels of resistance against a range of tobamoviruses.