Propranolol binding to human albumin (HSA) and to mixtures of alpha 1-acid glycoprotein (AGP) and HSA was examined in the presence of a perfluorochemical (PFC) blood substitute. The per cent free propranolol was determined using a dialysis exchange method at 37 degrees C. In 4% HSA solutions the per cent free propranolol was 51.9% and 53.6% at propranolol concentrations of 100 and 500 ng/ml, respectively. Buffer dilutions of 4% HSA solutions resulted in an increase in free propranolol. However, dilution of the HSA solutions with the PFC emulsion resulted in a significant decrease in free propranolol. In solutions containing 4% HSA with 0.067% AGP, the per cent free propranolol was 22.6% and 23.5% for 100 and 500 ng/ml propranolol, respectively. Again, the per cent free propranolol increased upon plasma protein dilution with buffer solution and decreased upon dilution with the blood substitute. A centrifugation method was utilized to determine the per cent bound propranolol associated with the PFC emulsion droplets in the presence of the proteins. Propranolol was significantly bound by the PFC emulsion even in the presence of a mixture of AGP and HSA. These results indicate that the overall affinity of the PFC blood substitute for propranolol is very substantial. Thus, administration of this PFC blood substitute may not result in the significant increase in per cent free propranolol normally associated with plasma protein dilution.