The objects of these experiments were to determine to what extent oleic acid, removed from plasma by forearm muscles, was oxidized immediately, and to search for evidence of an intramuscular lipid pool which may be composed of triglycerides synthesized from plasma free fatty acids and which may supply substantial portions of lipid substrates for oxidation by muscle. To these ends [1-w"C]oleic acid was infused at constant rate into the brachial artery of seven healthy young men at rest in the postabsorptive state. Results were: (1) muscle respiratory quotient (0.76) implied that about 80% of the oxygen consumed was for the oxidation of lipid. (2) Muscle free fatty acid uptake, had it been oxidized directly, could account for more than 100% of observed oxygen uptake.(3) There was a lag of at least 30 min before 'COn appeared in forearm venous blood. (4) "CO2 release from forearm muscle tended to reach an apparent plateau after 3 h of infusion of ["C]oleic acid. (5) During the time of plateau "CO2 release, oleic acid extracted from plasma could account for only 20% of oxygen consumption; most of the oleic acid taken up was not oxidized directly. (6) "CO2 release persisted at a high level during the 1-3 h follow-up period after the infusion ended. (7) Neither the delay in initial appearance of "CO2 nor its continued release after cessation of infusion was due to delay and distribution in a forearm COa pool, since intra-arterial infusion of Dr. Dagenais was a fellow of the Canadian Heart Foundation.Dr. NaH"CO3 in two additional subjects demonstrated much more rapid distribution of 'CO2 in the forearm. Results show that most, if not all, free fatty acids taken up by resting muscle are not oxidized directly, but probably enter an intramuscular pool which has a slow turnover during resting metabolism and is the immediate source of oxidized lipid substrate.