The frequency of antigen types (A, B, C, and DR) in an unselected group of 25 patients with chronic rheumatic heart disease and an unselected group of 15 patients with acute rheumatic fever was compared with that in a group of 100 healthy volunteers. All patients and controls were Arabs of Saudi origin. Only the frequency of HLA-DR4 was significantly different in the controls and the patient groups--controls 12%, chronic rheumatic heart disease 72%, acute rheumatic fever 53%, both patient groups together 65% (relative risk 13.6 with 95% confidence interval 10.5-16.7). Eighty three per cent of 12 patients with mitral stenosis and 70% of seven with aortic incompetence had HLA-DR4 antigen. In 17 non-Saudi Arab patients who had acute rheumatic fever or chronic rheumatic heart disease, the frequency of HLA-DR4 was identical (65%) to that in Saudi patients. These findings may have implications for the pathogenesis of rheumatic fever and rheumatic heart disease.