Platelet activating factor (PAF) is a phospholipid mediator of inflammation and stimulates anion secretion in animals and in isolated preparations of human colon. Nitric oxide (NO), synthesized from the amino acid L-arginine, is an important enteric inhibitory neurotransmitter. In addition, NO-donating compounds stimulate anion secretion in rat and guinea-pig colon. In this article, Angelo A. Izzo and colleagues review the key pharmacological features of the involvement of NO and PAF in the action of laxatives and propose that the classification of laxatives should take into account the important implications of these endogenous mediators.