When Christopher Columbus crossed the Atlantic Ocean in 1492, he brought together two worlds of infection which had developed in virtual isolation from each other for thousands of years. The picture of infectious disease in the New World differed from that in the Old World in many ways, but probably most dramatically in the absence or near absence of crowd infections capable of causing severe epidemics. The devastating effects of these crowd diseases in the post-Columbian period are well known, with conditions such as smallpox, diphtheria, measles, malaria, bubonic plague, yellow fever, and possibly typhus killing thousands of Native Americans, thus allowing inhabitants of the eastern hemisphere to become firmly established in the western hemisphere. Less is known about the diseases present in the Americas prior to 1492, but they probably included treponemal infections (pinta and syphilis), tuberculosis, forms of leishmaniasis and trypanosomiasis, fungal diseases such as coccidioidomycosis and paracoccidioidomycosis, various coccal infections, Rocky Mountain spotted fever, Lyme disease, legionellosis, hydatid disease, and a variety of intestinal parasite infections. It must be noted, however, that some of these syndromes were likely already present in both hemispheres in 1492. Recent research suggests that adult rheumatoid arthritis may also have its origin in the Americas. © 1992 Wiley-Liss, Inc.