Samples from 33 patients being treated with digoxin and three concentrations of control material were analyzed for this drug by use of seven radioimmunoassay (RIA) kits and an automated fluorescence polarization immunoassay (FPIA) system. CVs ranged from 2.4 to 6.4% for the FPIA system and from 4.6 to 7.4% for two RIA methods. In the analysis of between-method variability of RIA kits, CVs ranged from 6.1 to 33.2%. We compared each RIA kit with the other six RIA kits (I), as well as each RIA kit with the FPIA system (II). Correlation coefficients were greater than or equal to 0.96 in all cases. Slopes ranged from 0.82 to 1.20 for comparison I and from 0.86 to 1.01 for comparison II. For the FPIA system, analytical recovery of digoxin ranged from 94 to 104%. For the RIA methods we examined, analytical recoveries ranged from 113 to 135%. Analysis time is shorter and precision is greater for the FPIA system than for the RIA methods.