This study investigates the influence of heavy metals on ouabain-binding in presence of thiol (sulfhydryl) compounds. The data on in vitro effects of mercury (Hg), lead (Pb) and cadmium (Cd) showed significant inhibition of 3H-ouabain binding to microsomal membrane in a concentration-dependent manner. Maximum inhibition of 3H-ouabain binding was observed at 1 microM for Hg and 100 microM each for Pb and Cd. Preincubation with monothiol (L-cysteine or glutathione) or dithiol (dithiothreitol) protected inhibition of 3H-ouabain binding to the membranes by Hg or Pb. Dithiol but not monothiols partially protected Cd-inhibition. The present data confirm that the heavy metals interact with ouabain receptors in a manner similar to SH-blocking agents and protection of metal-inhibited 3H-ouabain binding by thiol compounds is metal specific.