Twenty-four hours after injection of carrageenan into one hind paw, injection of the same amount into the contralateral paw produced a significantly attenuated inflammatory response. However, when the second injection was given 7 days later, the inflammation induced in the contralateral paw was comparable with the initial response to carrageenan. A time-course study of carrageenan-induced inflammation in rats showed that significant oedema persisted 24 h after carrageenan administration and complete recovery was achieved in 7 days. The attenuated inflammatory response in the contralateral paw after 24 h was antagonized by bilateral adrenalectomy and chemical sympathectomy induced by 6-hydroxydopamine. Carrageenan-induced paw oedema was also significantly less in rats with subacute inflammation induced by the croton oil granuloma pouch technique. This attenuated response was antagonized by pretreatment of the rats with metyrapone, an inhibitor of adrenocorticoid synthesis, and by 6-hydroxydopamine. It is likely that the pre-existing acute or subacute inflammation attenuates the inflammatory response of carrageenan, by acting as a stressor, inducing activation of the sympatho-adrenal system.