Résumé : The present experiments were designed to assess the extent to which the β cell microtubular microfilamentous system contributes to the release of insulin evoked by glucose or sulfonylurea in the isolated perfused rat pancreas. Deuterium oxide (100%, v/v), which is thought to interfere with microtubular microfilamentous function, was found to suppress insulin release during both the early and late phases of the secretory process. The inhibitory effect of D 2O was reversible. When the pancreases were first exposed to cytochalasin B (10 μg/ml) and thereafter to both cytochalasin B and D 2O an escape phenomenon from the D 2O induced inhibition was invariably observed in response to either glucose or sulfonylurea. This escape phenomenon supports the view that the inhibitory effect of D 2O on insulin release is mainly due to a functional sideration of the microtubular microfilamentous system. The present data suggest, therefore, that such a system is actively involved in both phases of insulin release.