As a preface to the pharmacokinetic analysis of cocaine in pregnant and lactating rats (using oral administration of drug), young Long-Evans rats were used to compare the relative concentrations of cocaine in blood, brain, and liver after administering cocaine by iv or oral routes. Cocaine and its metabolites were determined using 3H-cocaine as a tracer, followed by homogenization and solvent extraction of tissues, and quantitative analysis by HPTLC and LSC. From 30 min postinjection to several hrs later, the concentration of cocaine was higher in brain (3-4 fold) and liver (3-5 fold) than in blood, using the iv route. Using the oral route, the concentration in brain was 2-3 fold higher than in blood, and in liver, 10-20 fold higher. The metabolites of cocaine were largely excluded from entry into brain tissue, whereas the accumulation of metabolites in liver was typically an order of magnitude higher, or more, than in blood (iv or oral route). The ratio of cocaine to metabolites increased in all three tissues, as the dosage increased, indicating that more and more of an administered dose actually reaches the tissues as cocaine as the dosage level increases. During the period from 30 to 90 min following the administration of cocaine to pregnant dams, cocaine appeared in fetal brain at a rate of 50-90% of the concentration in the dam's brain (presumably because of the lower lipid content in fetal brain compared to adult), but still at a rate of 109-151% of the concentration in the dam's blood. Cocaine is sufficiently stable in milk to assume that any cocaine entering breast milk from the blood stream will be available to the suckling infant, and after administering radioactive cocaine to lactating dams, the milk/blood ratio for cocaine averaged 7.8. These data indicate that both the fetus and suckling infant are at considerable risk from cocaine use by the mother.