The bioavailability of glipizide, plasma glucose, and insulin levels were measured in seven patients with non-insulin-dependent diabetes mellitus. Glucose and insulin response to three standard meals was measured at 11 identical time points on the day of placebo administration and on the first and 15th day of glipizide administration (mean dose of 8.7 mg glipizide orally per day). The bioavailability profile of glipizide was highly consistent between day 1 and day 15 of administration. On both days, the drug peaked within 1.2-1.8 h and displayed a plasma half-life of between 2.5 and 3.2 h. While insulin levels were significantly (P less than 0.05) increased at 4 of 11 time points of day 1, significantly elevated insulin levels were found at one time point on day 15 of glipizide administration. Insulin levels were found to be increased only in the presence of plasma drug concentrations of 200 ng/ml or greater. The hypoglycemic effect of the drug was significantly greater on day 15 than on day 1 of administration, and a significant hypoglycemic effect was noted even when drug levels were undetectable in plasma.