The aim of this 2 x 2 randomized double blind crossover study was to evaluate the effect of a single dose of clarithromycin on the pharmacokinetics of tolbutamide in nine healthy male volunteers. Each volunteer received orally 500 mg of tolbutamide, or 500 mg of tolbutamide and 250 mg of clarithromycin. The washout period between the two treatments was 7 days. Serum levels of tolbutamide were determined by HPLC. Serum profiles were analysed using a non-compartmental model. Blood glucose levels were also estimated using a glucometer (Ames) and Glucostix (Bayer). There was approximately 20% increase in mean absorption rate constant and 26% increase in mean bioavailability of tolbutamide in the presence of clarithromycin. A hypoglycemic effect was reported upon co-administration of the two drugs.