Thioridazine was administered to 14 patients diagnosed as within the “schizophrenic spectrum” with the result that substantial improvement in psychotic symptoms was achieved while significant extrapyramidal side effects occurred in only 1 patient. Under these conditions lumbar cerebrospinal fluid homo vanillic acid following probenecid was significantly elevated (48%). Cerebrospinal fluid probenecid and 5-hydroxyindoleacetic acid declined significantly during treatment with thioridazine. Taken in conjunction with the results of other studies, it appears that cerebrospinal fluid homo vanillic acid can be moderately elevated in man during successful treatment with antipsychotic drugs when extrapyramidal side effects are virtually absent. Possible interpretations of these results are discussed with regard to the clinical effects of antipsychotic drugs as they relate to central dopaminergic activity.