The second edition of Snow's inquiry was greatly expanded to include two maps – incidentally, the only two of his career. Snow intended this map of the water supply in South London to be the centrepiece of his study – often termed The Grand Experiment. It involved a mammoth on-foot investigation of 32 sub-districts of South London, supplied by two different water companies drawing water from different parts of the Thames – one polluted with contaminated water. Snow showed that those residents supplied by the polluted source were several times more likely to contract cholera. This demonstrated Snow's intuitive understanding of epidemiological principles: the groups exposed and not exposed to the contaminated water were very similar in every other respect, and large numbers were involved.

The experiment, too, was on the grandest scale. No fewer than three hundred thousand people of both sexes, of every age and occupation, and of every rank and station, from gentlefolks down to the very poor, were divided into two groups without their choice, and in most cases, without their knowledge one group being supplied with water containing the sewage of London, and, amongst it, whatever might have come from the cholera patients, the other group having water quite free from such impurity [...] To turn the grand experiment to account, all that was required was to learn the supply of water to each individual house where a fatal attack of cholera might occur ... When cholera returned in July of the present year, I resolved to spare no exertion which might be necessary to ascertain the exact effect of the water supply on the progress of the epidemic, in the places where the circumstances were so happily adapted for the inquiry'

—John Snow, On the mode of communication of cholera, 1855. p.76