We measured by RIA the serum and urinary digoxin-like immunoreactivity (EDLF) in 8 subjects with severe obesity and in 10 healthy, non-obese individuals (as a control group), to evidentiate whether circulating and urinary levels of EDLF are increased in obesity. For each individual, we measured the mean EDLF on two sera collected consecutively on two successive mornings, between 8-9 a.m. and the daily urinary EDLF excretion. Every subject collected his/her 24 hour urine in 5 different timed fractions. For each urine fraction, we measured the excretion of EDLF, electrolytes (Na and K), and creatinine. In obese people, the mean serum digoxin-like immunoreactivity (no. 8, 27.3 +/- 8.7 ng/L de) was significantly higher (unpaired t test, p = 0.0002) than in the controls (no. 10, 12.0 +/- 7.3 ng/L de), whereas control and obese subjects had superimposable 24 hour EDLF urinary excretion. Urinary excretion of EDLF significantly changed throughout the day in normals, but not in obese people. In a multiple stepwise regression analysis, urinary K+ and Na+ significantly (p less than 0.01) contributed to the regression with urinary EDLF (EDLF = 76.9 + 0.67 K+ - 0.24 Na+; R = 0.601, no. 40) in obese individuals. The in vivo kinetic and metabolic pathways of EDLF are conceivably different in obese and normal subjects. A difference in the production rate, binding to plasma proteins and/or removal mechanisms could explain the findings of higher circulating levels with normal EDLF urinary excretion in obese persons.(ABSTRACT TRUNCATED AT 250 WORDS)