Cell mediated immunity to flagellin was tested for by delayed hyper-sensitivity (DHS) skin reactions in man, guinea-pig and rabbit, and by production of macrophage migration inhibition factor (MIF) in man. In most humans, there was a cutaneous reaction to intradermal flagellin which was not classical tuberculin type DHS, but was a ‘delayed in time’ reaction commencing at 3–6 h, peaking at 24–30 h and waning by 48 h; histologically there was a mild non-specific polymorph and mononuclear cell reaction in the dermis. The reaction was much smaller after a second challenge with flagellin. Five subjects who produced minimal or no humoral antibody to flagellin displayed a classical DHS reaction. Lymphocytes from subjects immunized with flagellin could not be shown to produce MIF. DHS reactions to flagellin were not demonstrated in the guinea-pig or rabbit. The cutaneous reaction to flagellin in man was interpreted either as true DHS modified by antibody, or a type of Jones-Mote reaction not equatable with that associated in the guinea-pig with cutaneous basophil hypersensitivity.