Orosensory exposure to dietary fat elicits an early, transient spike (first phase; minutes 0-60) and augmented, more sustained postprandial (second phase; minutes 120-360) elevation of serum triacylglycerol (TAG) in humans. To assess the physiological significance of these effects, TAG concentrations were monitored following manipulation of the oral exposure pattern and accompanying lipid load. Fifteen healthy adults participated in a randomized, 6-arm, crossover design study. Conditions consisted of ingestion of 30-g loads of safflower oil, provided as capsules to bypass oral stimulation, followed by 15 min of oral stimulation (mastication and expectoration) with full-fat or nonfat cream cheese (conditions 1 and 2); the same oral load ingested intermittently with oral stimulation by both food forms (conditions 3 and 4); and 10-g lipid loads ingested with intermittent oral stimulation by both food forms (conditions 5 and 6). Blood was collected via an indwelling catheter and TAG was measured at minutes -15, 0, 10, 20, 30, 40, 50, 60, 120, 240, and 360 relative to the onset of sensory stimulation. Testing was conducted weekly. Sequential (lipid loading followed by oral stimulation) and intermittent (intermixed lipid loading and oral stimulation) conditions led to comparable TAG responses. Significant first- and second-phase TAG concentration increases were observed with the 30-g loads, but not the 10-g loads. TAG responses to the full-fat and nonfat stimuli were similar. These data support the veracity of the earlier literature based on sequential oral exposure regimens and indicate that TAG responses reflect an interaction between oral fat signaling and gut lipid content. The augmentation of TAG associated specifically with dietary fat exposure, as compared to a nonfat food matched on other sensory properties, may only occur with higher fat loads.