gamma-Oxo(1,1'-biphenyl)-4-butanoic acid (fenbufen) and biphenylacetic acid have effects on platelets similar to other non-steroidal antiinflammatory agents. In vitro biphenylacetic acid (BPAA), a metabolite of fenbufen, is more potent than fenbufen and in vivo metabolism of fenbufen to BPAA is probably required for activity. The arachidonate-thromboxane system appears to play a critical role in explaining a major part of the mechanism of action of these agents on platelets and other systems. Fenbufen, however, also inhibits collagen-induced platelet aggregation without requiring metabolic conversion to BPAA. The mechanism for this inhibition appears to be independent of the arachidonate-thromboxane system, as well as unrelated to serotonin release or inhibition of phosphodiesterase activity. The effects of fenbufen and BPAA on platelet biochemistry and function suggest their utility as clinical anti-thrombotic agents. This is further supported by the absence of any thrombocytopenia or bleeding tendency in animals and man.