beta cells in islets of Langerhans were studied in Sprague-Dawley rats dosed by gavage with 0 (control), 75, 150, 250 or 300 mg/kg body wt/day S-H 966 BS [1-(1-oxido-4-thiomorpholino)-3-(1-piperazinyl)], an isoquinoline derivative. All doses caused a significant and dose-dependent increase in serum glucose (diabetes mellitus). At 250 mg/kg, degranulation of beta cells was discovered after 1 day and vacuole formation after 2 days. Ultrastructural alterations compared well with that seen after treatment with cyproheptadine and other structurally related compounds. The vacuolation of beta cells was fully developed following 6 weeks of daily treatment, when a dose-dependent elevation of blood glucose was first observed. The effects were more severe in males than in females. Lesions were reversible within 6 weeks except at 300 mg/kg in males.