We have shown that ethanol and certain other drugs impair folate metabolism in man. We have also studied changes in folate metabolism and in folate binding in uremia, cancer, and liver disease. We propose to identify the mechanism by which ethanol lowers serum folate level and to explore possible mechanisms by which diphenylhydantoin causes folate deficiency in man. We will evaluate with microbiologic assays and radioassay the effect of standardized meals, short-term fasting, and short-term ingestion of ethanol or diphenylhydantoin on folate metabolism in volunteers, concentrating on transport, cellular uptake, and urinary excretion of folate. We also hope to elucidate the biologic significance of elevations in serum levels of unsaturated folate binding protein in cancer, granulomatous disease, and alcoholic liver disease. The overall objective of our research is to learn how certain drugs and diseases impair folate metabolism in man.