The rate of alcohol absorption is dependent on gastric emptying (GE). As the slowing of GE by fat is dependent on lipolysis, orlistat may increase the rise in blood alcohol when alcohol is consumed with, or after, fat. The aim of the study was to evaluate the effects of orlistat on GE and blood alcohol after an alcohol-containing drink following a fat 'preload', in healthy subjects. Ten healthy males consumed 120 ml cream with or without 120 mg orlistat, 30 min before an alcohol-containing drink labelled with 20 MBq [(99 m)Tc]sulfur colloid on 2 d. GE, plasma alcohol and blood glucose were measured. GE was slightly faster with orlistat (P<0.05) compared with control. Plasma alcohol at 15 min was slightly higher with orlistat (0.034 (SEM 0.006) g/100 ml) v. control (0.029 (SEM 0.005) g/100 ml) (P<0.05), but there was no effect on the area under the curve 0-240 min. The increase in blood glucose was greater with orlistat, for example, at 15 min (1.07 (SEM 0.2) mmol/l) v. control (0.75 (SEM 0.2) mmol/l) (P=0.05). The rise in blood glucose and plasma alcohol were related (for example, at 15 min r 0.49; P=0.03). In conclusion, lipase inhibition accelerates GE of an alcohol-containing drink following a fat 'preload' with a minor increase in the initial rise in plasma alcohol.