The effect of nicotine on the bioformation of prostacyclin (PGI2) and of thromboxane (Tx)B2 in rabbit aorta and platelets, respectively, was investigated. Rabbit aortic rings were incubated with [14C]-arachidonic acid ( [14C]-AA) and the incubation products were separated with thin layer chromatography (t.l.c.). Alternatively, the aortic rings were incubated without substrate and their spontaneous formation of platelet anti-aggregatory activity was measured. Rabbit platelet microsomes were incubated with [14C]-AA and the products formed were separated with t.l.c. Rings of aorta were found to be incapable of converting added [14C]-AA to labelled 6-keto-PGF1 alpha (the stable hydrolysis product of PGI2). Rings of aorta incubated in saline medium spontaneously formed PGI2-like activity. This formation was dose-dependently inhibited by nicotine, with an I50 of about 10(-4) M. Platelet microsomes converted [14C]-AA to labelled TxB2. This formation was unaffected by nicotine. It is concluded that a true difference in sensitivity to nicotine exists between cyclo-oxygenase in rabbit aorta and platelets. The data also demonstrate a tissue difference between rabbit aorta and platelets concerning their utilization of exogenous AA as substrate in the formation of platelet active compounds.