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A detailed study of salicylate binding to human serum albumin was undertaken because of the widespread use of the drug, its deleterious effect on fetal development (in the laboratory animal) and its well-documented adverse effects on neonatal well-being. Serum was obtained from 82 patients during each trimester of pregnancy, labor, 4 days and 6 weeks post partum. Equilibrium dialysis at 4 °C was carried out utilizing therapeutic levels of 14C-labeled sodium salicylate. Scatchard plots were employed to translate the data into association constants (k:) which characterized the binding affinity between salicylate and albumin. At the primary binding site, the mean k' values were: controls (nonpregnant females) 40, first trimester 32, second trimester 28, third trimester 26, labor 15.5, 4 days post partum 18.4, and 6 weeks post partum 37.6 x 104 M^-1 These results demonstrate a decrease in the binding affinity between salicylate and serum albumin as pregnancy proceeds to the puerperium, at which time the binding affinity increases to near control values at 6 weeks post partum. The increased concentration of free (unbound) salicylate would be readily available for transplacental transport to exert an effect upon fetal receptors. The changes found may be attributable to competitive or allosteric binding of endogenous compounds such as hormones, characteristic of the normal physiology of pregnancy.