To characterize the role of fatty acid oxidation in the control of food intake, we investigated the effect of 2-mercaptoacetate, which inhibits fatty acid oxidation, on meal patterns and cumulative food intake in rats. Rats were fed either a medium fat (MF, 18% fat) or a low fat (LF, 3.3% fat) diet. Mercaptoacetate (400 mumole/kg body wt), intraperitoneally injected in the middle of the bright or at the onset of the dark phase of the diurnal lighting cycle, increased cumulative food intake in MF rats by shortening the latency to eat after injection and the duration of the subsequent intermeal interval (IMI) without affecting the size of the first meal. Mercaptoacetate, injected in the middle of the bright phase, reduced the latency to eat but did not affect the duration of the subsequent IMI or cumulative food intake in LF rats. A higher dose of mercaptoacetate (600 mumole/kg body wt), initially increased and later decreased cumulative food intake in MF rats. The initial increase in food intake was due to shorter IMIs; the subsequent decrease in food intake was due to smaller meals after mercaptoacetate injection than after control injection. The results indicate that a drop in fatty acid oxidation caused by mercaptoacetate triggers a meal. This implicates fatty acid oxidation in the maintenance of postprandial satiety.