Spurred on by the great immunochemists of the early twentieth century, immunologists acted for many years as though one antigen was as good as another. Antigens wmere used because they were cheap or convenient, so we learned a lot about the properties of immunity to materials such as sheep red blood cells, egg albumin, dinitrophenol, and so on. What immunologists found out, of course, was tremendously important, and most of the principles that are the foundation of modern immunology were learned with these models. This course of action, however, was to some extent misleading, because the fact of the matter is that, in real life, most infectious organisms have spent their millions of years of coevolution with the immune system developing mechanisms of manipulating the system. The upshot is that no invading organism behaves exactly like a sheep red blood cell and, if immunologists really w# ant to understand how infectious diseases interact with their hosts, they have to study the disease and host themselves. Artificial substitutes simply will not do. The goal of the invading organism, like that of the rest of us, is to propagate itself. Organisms whose lifestyle depends upon colonizing another individual have several obstacles to overcome in order to achieve their objective. They must find a niche in their host that they can occupy for the time required for reproduction. Their physiology must match that of their hosts, in that they must be able to salvage the metabolites they need from their host. For the period required to complete their cycle, they must be able to evade the defense mechanisms of the individual they have colonized. This last requirement poses something of a Catch-22 to the invader. On the one hand, the invader must be protected against rejection, but on the other hand, the host must not be so incapacitated that it dies of overwhelming infection, either by the invader itself or by other organisms before the requirements of the invaders have been met. Moreover, the defense mechanisms must not be so incapacitated as to allow colonization by other organisms that might outcompete the original occupant.