Through a series of controlled experiments in volunteers, quantitative aspects of infection, illness, and immunity to ECHO-11 virus were studied. ECHO-11 is a transmissable viral infection in man and equally infectious to the upper respiratory and the intestinal tracts. The rate of infection was directly related to the dose of virus exposure, but any infectious dose of virus produced illness in only about one-third of the infected subjects. The infectious dose for man varied over a billionfold range. Larger challenge doses caused no difference in the local symptoms at the portal of entry or in the peak severity of illness, but symptoms were more diverse and prolonged after a higher dose. Persons with asymptomatic infections became just as heavily infected as ill persons. In respiratory secretions from natural infection, the titer of infectious virus was found to be about 10(2) median infective doses in tissue culture (TCID(50))/ml. At this level, up to 40% of exposed contacts could be infected per milliliter of secretion. The observed rate of spread was 24%. This low-dose inoculum caused illness in 12% of volunteers but failed to elicit a significant antibody response in 93% or immunity to reinfection and another illness upon rechallenge. Larger doses of virus produced a longer excretion of virus and a significant increase in serum-neutralizing antibody. Nasal antibody was infrequently found. The principal effect of antibody was to decrease virus excretion and to shorten illness; it reduced the rate but did not prevent infection. Attempts to produce an asymptomatic enteric infection which would induce immunity failed.The characteristics of respiratory transmission with mild disease, recurrent infection, and illness without a detectable antibody response or solid immunity to reinfection, satisfy the epidemiologic conditions to establish ECHO-11 virus as one of the causes of the common cold.