Among the most prominent opponents of vaccination were two members of the medical profession, one more eminent than the other. Edgar Crookshank, Professor of Comparative Pathology and Bacteriology and Fellow of King's College, London, wrote a History and Pathology of Vaccination in two volumes (1889). The Preface to the first volume described how, following some investigations into an outbreak of cowpox, he became convinced that

The essence of Crookshank's argument against vaccination was that the power of conferring immunity to smallpox, claimed for cowpox by disciples of Jenner, was a fallacy because what was injected under the guise of cowpox was in fact smallpox. The origins of this controversy lay in the earliest period when, with supplies of cowpox very scarce for lack of suitable outbreaks to draw on, some confusion had occurred over a consignment of alleged cowpox despatched by Jenner from London to a colleague in the country. Detractors claimed that, whether by accident or from lack of scruple, Jenner had in fact supplied his friend with smallpox lymph, and that since the material in question had formed the basis for thousands of ‘ingrafting’ operations carried out from arm to arm right down to Crookshank's own time, any immunity ascribed to cowpox should really be ascribed to the effects of smallpox. This theory was revived in recent times but has been investigated by Baxby who finds no basis for it.

Crookshank's general conclusion as a result of his investigation was that the medical profession had been misled by Jenner, by his biographer, Baron, by the Reports of the National Vaccine Establishment and by a want of knowledge concerning the nature of cowpox, horsepox and other sources of ‘vaccine lymph’: