Plasma and urine concentrations of amygdalin, whole-blood concentrations of cyanide, and thiocyanate concentrations in serum and urine were determined in cancer patients following intravenous (4.5 g/m2) and oral (500-mg tablet) administration of amygdalin. To measure low plasma concentrations of amygdalin following oral administration a GC/MS assay was developed. Following intravenous administration, concentrations of parent drug as high as 1,401 microgram/ml were observed, with no increase in plasma concentrations of cyanide or serum concentrations of thiocyanate. Plasma elimination of amygdalin was best described by a two-compartment open model with a mean distributive phase half-life of 6.2 min, mean elimination phase half-life of 120.3 min, and mean clearance of 99.3 ml/min. Following oral administration of amygdalin, plasma concentrations were much lower, with peak values of less than 525 ng/ml. Cyanide concentrations increased to values as high as 2.1 microgram/ml whole blood. Thiocyanate concentrations did not increase for several days, plateauing at values as high as 38 microgram/ml serum. Ingestion of almonds by two patients taking oral amygdalin increased cyanide concentrations compared with values obtained after oral amygdalin alone.