During the incubation of arachidonic acid with platelet-rich plasma, a persistent activity appeared that caused the release of [14C]5-hydroxytryptamine from indomethacin-treated platelets. By the time-course of its appearance and disappearance, this release-inducing activity could be dissociated from prostaglandin endoperoxides and associated with thromboxane A2-like material. This material persists in plasma because of its continued production and increased stability.