1. Serum immunoreactive insulin, glucose tolerance and growth hormone levels were estimated in healthy volunteers before and after receiving diphenylhydantoin sodium (DPH) for 14 days.
2. With a standard oral dose of DPH all subjects showed a reduced insulin response to oral glucose (11–44%). This correlated with the serum concentration of the drug, which ranged from 30.5 to 90.0 μmol/l (7.7–22.7 μg/ml).
3. Glucose tolerance remained normal and no changes in growth hormone levels were observed.
4. Different doses of DPH have been employed in the treatment of insulinoma and as a screening test for detecting latent insulin secretory defects. This study confirms the wide inter-individual variation in the metabolism of DPH, and stresses both the importance of measuring the serum concentration of DPH and the comparative irrelevance of dosage levels in these situations.