Escherichia coli endotoxin instilled intranasally into mice and rats caused a severe pulmonary oedema associated with progressive increases in lung weights of up to 30% within 2 days. When mice were injected with DDT (20 mg/kg) 20 and 2 hr prior to the administration of endotoxin the animals were found to be tolerant to the endotoxin. The inflammatory oedema induced by endotoxin is caused by release of lung histamine, and as DDT injections also lowered histamine content in the lungs, the protective effect of DDT against the oedema induced by endotoxin appears to be due to its prior depletion of the lung histamine stores. An opposite effect, increased and accelerated inflammation, was observed by chronic exposure of rats to dietary DDT (150 ppm) fed for 36 days. The long-term feeding of DDT is known to cause adaptations in many physiological systems. One of these may be increased histamine synthesis and subsequently increased severity of histamine mediated reactions.