Palmitoyl-CoA hydrolase [EC 3.1.2.2.] activity in rat liver was found to be enhanced by high fat diets. Partially hydrogenated marine oil and high-erucic acid rapeseed oil diets produced a greater increase than a diet containing soybean oil. With diets containing from 5 to 30% (w/w) of partially hydrogenated marine oil the increase in palmitoyl-CoA hydrolase activity was similar to the increase observed in peroxisomal beta-oxidation activity (correlation coefficient r = 0.94). A positive correlation (r = 0.86) also was observed between the activity of palmitoyl-CoA hydrolase and previously determined levels of long-chain acyl-CoA. The results presented may suggest a common "induction" mechanism for palmitoyl-CoA hydrolase and peroxisomal beta-oxidation enzymes, possibly exerted through an increased cellular level of long-chain acyl-CoA.