The effect of food on the oral bioavailability of a manidipine 20 mg tablet was studied after a single administration in 12 male healthy subjects. The clinical trial was conducted as an open, randomised, crossover study. In two different administration sessions, the subjects received a 20 mg manidipine tablet either in the fasting state or after a standardized breakfast. Plasma samples were collected before and at different times after each administration for up to 24 h. The concentrations of manidipine and its pyridine metabolite (M-XIII metabolite) were determined by HPLC with coulometric detection. The tolerability of manidipine was good. Only two cases of mild headache, one with each treatment, were reported. Food significantly improved the absorption, with an increase in AUC from 19.1 to 27.2 ng.h/ml (geometric mean, p<0.01) but did not modify the rate of absorption (tmax unchanged, median = 1.5 h). Peak plasma concentration was also increased (from 6.2 to 7.8 ng/ml), but the difference was not statistically significant (p=0.18). Other pharmacokinetic parameters (apparent elimination half-life and mean residence time) remained unchanged. The increase in bioavailability of manidipine administered with food is related to its high lipophilicity and may be explained through a solubilization effect produced by food and bile secretions.