Cryogenine was effective in limiting the development of artificially induced inflammatory responses in acute and chronic experiments in rats. Cryogenine altered the acute edematous reaction to plantar injection of carrageenin and inhibited development of increased foot thickness induced by plantar injection of nonviable mycobacterial adjuvant in chronic studies. Histopathologic examinations did not suggest actions that would interfere with the anti-inflammatory evaluations. Cryogenine demonstrated a low order of analgesic (rat tail flick) and antipyretic (peptone fever) activity, and was capable of partially reversing edema and pain produced by silver nitrate injections in the ankle joints of rats. Cryogenine blocked serotonin, bradykinin, and histamine responses in guinea pig ileum; and pretreatment limited serotonin-induced pedal edema in rats and blocked histamine-induced intradermal wheals in the rabbit. Cryogenine was ineffective as a fibrinolytic agent. Prototype nonsteroidal anti-inflammatory compounds as well as agents with structural similarities to cryogenine were also investigated. Cryogenine may, like aspirin, manifest its anti-inflammatory activity through a combination of selective central and nonspecific peripheral mechanisms.