Two cross-over studies were carried out in 23 patients with Type 2 diabetes, to examine whether glipizide, a potent sulphonylurea with fast and complete absorption and rapid elimination (t1/2 less than 5 h), can be given once-daily without loss of therapeutic effect. In both studies, patients were randomly assigned to an initial dose of 7.5 mg once daily or 2.5 mg three-times daily, which was increased to 15 mg o.d. or 5 mg t.i.d. if the fasting plasma glucose remained over 10 mmol/l on the lower dosage. In Study 1 (n = 11), administration once a day before breakfast was compared with intake before breakfast, lunch and early dinner (5 p.m.) and in Study 2 (n = 12) the comparison was between intake once-daily before breakfast and dosing before breakfast, lunch, and at bedtime (10 p.m.). Neither the 24-hour urinary glucose excretion nor HbA1, fasting plasma glucose, insulin or C-peptide levels differed between the once and three times daily administration with the third dose given before early dinner. The nadir plasma levels of glipizide were not significantly different and were often too low to be detected. Postponing the third dose until 10 p.m. did not produce any improvement in HbA1 or in fasting plasma glucose, insulin or C-peptide. The mean nadir glipizide levels following this schedule were twice as high as those after once-daily administration. As expected, the plasma glipizide after breakfast was higher when the whole dose was taken before breakfast than when it was divided. The corresponding plasma level of insulin was higher and that of plasma glucose was lower.(ABSTRACT TRUNCATED AT 250 WORDS)