In an experimental investigation of the chemotherapy of intracranial infections, we have made a preliminary study of the effects of the sulfonamide drugs on the normal dog's brain. The development of convulsions in a very high percentage of animals following the intracranial implantation of sulfathiazole prompts this preliminary report, as a warning against the clinical use of this drug in this manner. In this study, varying doses of three drugs (sulfanilamide, sulfathiazole and sulfadiazine1) were placed on the brains of normal dogs under intravenous anesthesia with soluble pentobarbital. The dura mater was closed over the drug. Subsequent determinations of the concentration of the respective drugs in cerebrospinal fluid and blood were made at frequent intervals, clinical findings were recorded, the animals were killed after varying periods and specimens of dura mater and brain were obtained for microscopic study. In control experiments, two additional procedures were employed: the same operation