Orlistat (O) is a potent and selective inhibitor of gastrointestinal lipases. The effect on dietary fat absorption following dosing of O at different times relative to meals was investigated in a placebo (P) controlled study in 24 hospitalized healthy males. After a 5-day run-in, to accustom the subjects to a diet of 2400 kcal and 77 g fat per day and to establish baseline faecal fat excretion, subjects received, in four parallel groups of 6. over 8 days three times daily doses of 80 mg O.P.P (group A) or P. 80 mg O.P (group B) or P.P. 80 mg O (group C) or P.P.P (group D) at mid-meal. 1 h and 2 h after mid-meal respectively. Faeces were collected to measure total fat excretion. The mean (s.d.) of faecal fat in percent of dietary fat, after deduction of pre-treatment faecal fat, was (%) 32.8 (8.1), 34.0 (8.8), 26.9 (4.0) and -1.4 (1.7) in groups A. B. C and D respectively. It was concluded that, within the time period investigated, the pharmacological effect of O is not critically dependent on the time of dosing relative to meals.