The authors studied the glycemic disturbances provoked by two antihypertensive drugs, propranolol and hydrochlorothiazide, administered alone or in combination to normal and diabetic rats, using biochemical and ultrastructural parameters. It was found that hydrochlorothiazide raised fasting glucose concentration significantly; propranolol alone caused an insignificant rise of glucose, but significantly aggravated the effect of hydrochlorothiazide with an additive interaction. The ultrastructural findings, as well as the urinary C-peptide excretion, confirmed that the glycemic effects should not be thought to be due to a direct action of the drugs used on the endocrine pancreas.