Due to the inhibition of beta-oxidation, radiolabeled long-chain fatty acids with substituents in the alkyl chain often can enhance the retention of myocardial radioactivity. In this connection the synthesis and biodistribution of 12 new radioiodinated omega-(p-iodophenyl)fatty acids is described featuring a p-phenylene group as an inhibiting group. Phenyl fatty acid esters were acylated (Friedel-Crafts) with omega-(p-halophenyl)fatty acid chlorides, reduced and hydrolyzed (Wolff-Kishner) to form the omega-(p-halophenyl)-p-phenylene-fatty acid (PHIPA) derivatives. The peak heart uptake and the loss of radioactivity from the myocardium of fasted Sprague-Dawley rats depended on the alkyl-chain length and p-phenylene position. Thus, compared to radioiodinated 15-(p-iodophenyl)pentadecanoic acid (IPPA) some of the 131I labeled PHIPA derivatives with 12, 13 or 14 methylene groups proved to show an about equal initial heart uptake (about 5% inj. dose/g at 2.5 min). This was especially true for those PHIPA derivatives with a p-phenylene moiety close to the carboxylic acid group. The retention of radioactivity in the heart was also significantly prolonged when the p-phenylene group was in this position. Among the PHIPA derivatives investigated, 13-(p[131I]iodophenyl)-3-(p-phenylene)tridecanoic acid (PHIPA 3-10) and 14-(p-[131I] iodophenyl)-4-(p-phenylene)tetradecanoic acid (PHIPA 4-10) showed the most promising characteristics for potential use as new myocardial imaging agents. Both agents showed an initial heart/blood activity ratio of about 10 which increased to 15 after 10-30 min. This high value was maintained for at least 4 h.