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OBJECTIVE:: To examine the short-term effects of a lipase inhibitor (Orlistat) on physiological and behavioural measures of appetite in response to a high-fat meal. DESIGN:: Randomised, single blind, placebo-controlled, crossover trial. SUBJECTS:: A total of 19 healthy nonobese male subjects. PROCEDURES:: After an overnight fast, subjects ingested a test meal of 2940?kJ (60% fat, 30% CHO, 10% protein) with Orlistat (120?mg) or a placebo, separated by 2 weeks. Appetite, as assessed by a standard line scale, and plasma cholecystokinin (CCK) concentrations were measured prior to and every hour after the test meal for 4?h. Thereafter, subjects ingested a quantified, but self-selected portion of a standardised lunch (15% protein, 37% fat and 45% CHO), before completing a final line scale questionnaire. RESULTS:: The CCK response to the test meal was negatively correlated with BMI in both the Orlistat and placebo trials (R=-0.69 and -0.65, P<0.01). Orlistat administration did not significantly alter the CCK response to the test meal (6.30±3.27 vs 7.36±3.94?pM?min, for Orlistat and placebo, P=0.193). Similarly, the line scale measures of appetite and subsequent intake (520±205 vs 554±197?g, P=0.48) were not different between the trials. CONCLUSION:: Orlistat administration did not alter short-term physiological or behavioural measures of satiety in response to a high-fat meal in healthy, nonobese subjects. The CCK response to a test meal may be partly determined by BMI.International Journal of Obesity (2003) 27, 1479-1485. doi:10.1038/sj.ijo.0802436 [ABSTRACT FROM AUTHOR]