To search for a genetic marker in patients with thyrotoxic periodic paralysis (TPP), we studied the erythrocyte sodium-potassium pump activity in 13 patients with TPP; 30 thyrotoxic patients with no history of paralysis (T) and 69 euthyroid controls. In thyrotoxic patients (TPP and T), erythrocyte ouabain binding and ouabain sensitive sodium efflux rate constant were decreased while erythrocyte sodium content was increased. All these changes reverted to normal when the patients became euthyroid. Maximal ouabain binding capacity correlated positively with ouabain sensitive sodium efflux rate constant (r = 0.542; p less than 0.001; n = 155) and negatively with serum thyroxine concentration (r = -0.571; p less than 0.001; n = 60) and erythrocyte sodium content (r = -0.521; p less than 0.001; n = 155). In the thyrotoxic state, maximal ouabain binding capacity was just significantly higher in TPP when compared with T (0.268 +/- 0.014 and 0.234 +/- 0.009 pmol/10(9) cells respectively; p less than 0.05). This difference could not be demonstrated when the patients became euthyroid. Our findings suggest that patients with TPP respond to thyrotoxicosis with a smaller decrement in erythrocyte sodium-potassium ATPase activity than patients without a history of paralysis. However, the difference is too small to represent a useful genetic marker for this disease entity