Summary: The brain uptake of phenobarbital during pro longed status epilepticus (3 h) was studied in paralyzed, ventilated sheep. The first 30 min of status epilepticus was characterized by systemic hypertension, increased CBF, increased peripheral vascular resistance, a fall in brain pH, and an elevation in brain lactate concentra tions. Subsequently, hemodynamic factors normalized and brain acidosis persisted. Phenobarbital administered during the early phase of status epilepticus produced higher levels of brain phenobarbital concentration, which was greatest at the earliest sample time (5 min followingThe kinetics of anticonvulsant medications ad ministered during status epilepticus are poorly un derstood. Metabolic perturbations during status epilepticus, e. g. , alteration of blood-brain barrier (BBB) permeability (Petito et aI. , 1977), ictal hy pertension (Johansson et aI. , 1970; Suzuki et aI. , 1984), hypoxia (Suzuki et aI. , 1983), hypercapnia (Johansson and Nilsson, 1977), systemic corticoste roid and catecholamine release (Long and Holaday, 1985), as well as the effect of the drug itself (Jo hansson, 1983) may influence brain uptake of anti convulsants. Recently, the influence of the blood brain pH gradient on brain uptake of the weak acid phenobarbital (Simon et aI. , 1985) and the weak base lidocaine (Simon et aI. , 1982; Simon et aI. , 1984) during bicuculline-induced status epilepticus