The frequency of hypertrophic osteoarthropathy in cyanotic congenital heart disease has previously been considered to be very low. Only a few isolated reports have described such an association. We studied 32 consecutive patients older than 6 years with various types of cyanotic congenital heart disease and examined each case for hypertrophic osteoarthropathy. We also assessed the role of the altered cardiopulmonary hemodynamics in the development of hypertrophic osteoarthropathy by means of cardiac catheterization. Our results showed that 31% of the patients had hypertrophic osteoarthropathy. When the hemodynamic parameters of the group of patients with hypertrophic osteoarthropathy were compared with those of the remaining patients, we found significant differences in the systemic blood flow (P less than or equal to 0.05), right-to-left shunt (P less than or equal to 0.05), and arterial oxygen unsaturation (P less than or equal to 0.005). Thus, we found a much higher prevalence of hypertrophic osteoarthropathy in patients with cyanotic congenital heart disease than has previously been recognized. The development of hypertrophic osteoarthropathy is related to the degree of bypass of the lung. This is consistent with the concept that hypertrophic osteoarthropathy results from mediators in the systemic venous circulation that escape inactivation in the pulmonary capillary bed.