Digoxin-like substance (DLS) is detected in pregnant women near term, newborns, and in patients with renal failure using RIAs for digoxin. We made "digoxin" measurements in such patients using three digoxin RIA kits (Nuclear Medical Laboratories (N), Clinical Assays (C), and Corning Magic (M]. At term mother DLS (micrograms/l digoxin) was 0-0.19 (N), 0.09-0.24 (C), 0.07-0.24 (M); cord blood DLS was 0.35-0.75 (N), 0.46-0.90 (C), 0.42-0.90 (M); infant DLS was 0.5-1.1 (N), 0.28-0.98 (C) and was not measured by M. DLS was detected at term in mothers and was essentially undetectable by 24 hr postdelivery. Cord levels fell in eight of ten infants to significantly lower levels by the second day of life. DLS in renal hemodialysis patients not receiving digoxin was 0.04-0.41 (N), 0.01-0.34 (C), 0.03-0.40 (M). While postdialysis levels by N tended to be lower than predialysis, they rose by C and M. Dilutions of cord blood yielded similar results by N, nonlinear decreases by C, and more nearly parallel decreases by M. In renal failure patients, dilutions yielded similar results by N and marked nonparallel results by M. Digoxin results obtained with immunoassays may be inaccurate in these patient populations. Digoxin immunoassays must be individually characterized as to the expected results.