In their article investigating digoxin measurements in the presence of Digibind®, Ocal and Green (1) conclude that “useful free digoxin concentrations may be obtained for Digibind-treated patients using either the AxSYM or Stratus immunoassays… ”. Yet they cite several references that report that digoxin concentrations measured with the Stratus® instrument were significantly higher than were free digoxin concentrations measured after ultrafiltration (2)(3)(4)(5). The AxSYM® assay has also been shown to yield higher results than ultrafiltration (6). These studies contradict the assertion that the AxSYM and Stratus assays are measuring free digoxin concentrations. Nonetheless, one can agree that results from the Stratus II and AxSYM may be suitable for monitoring the course of Digibind treatment. To use these results most effectively, one must understand their limitations and the probable sources of the discrepancy with ultrafiltration results. The results of previous investigations, as well as binding kinetics theory, suggest that these immunoassays will overestimate the free digoxin concentration. The extent of overestimation will vary with the extent of digoxin binding to albumin, with the assay measurement strategy, and with the absolute and relative amounts of digoxin and Digibind in the specimen. In most instances, the extent of the overestimation will be small enough that the result can be quite informative. In particular, these results set an upper limit on the concentration of pharmacologically active digoxin and can be used to rule out recurrent toxic concentrations. One reason that the Stratus and AxSYM assay results exceed free digoxin concentration is that they are designed to measure total digoxin in routine specimens, including digoxin bound to serum proteins, principally …