To compare the pharmacokinetic and pharmacodynamic effects of glimepiride between once- and twice-daily dosing in type 2 diabetic patients. Eight Japanese type 2 diabetic patients, who had been treated with 2 mg glimepiride alone over 4 weeks (age 40-70, body mass index <or=25 kg/m2, hemoglobin A 1C<8.0%), were randomly assigned to the crossover study with glimepiride 2 mg once-daily and 1 mg twice-daily for 4 weeks for each regime. Serum concentrations of glimepiride, plasma glucose, insulin and C-peptide were measured over 24 h at the fixed time intervals on the last day of each crossover period, and HbA 1C was measured at the same day. Pharmacokinetic profiles in two regimens were different to each others; a single peak of serum glimepiride concentration was observed in once-daily, and double peaks in twice-daily dosing. Drug concentration increased immediately, and peaked at 2 h after administration irrespective of dosage. Cmax value in once-daily dose was higher than those in twice-daily doses. AUC values were not different between two regimens. Pharmacodynamic profiles for plasma glucoses, serum insulin and C-peptide showed no statistically significant differences between two regimens, and parameters were not different each other. Analyses of adverse events and laboratory data demonstrated a favorable safety profile of glimepiride. The present results suggest that glimepiride may be suitable for once-daily dosing with respect to clinical usefulness.