To assess its hypolipidemic predictive value, maximally induced low density lipoprotein receptor activity was measured in vitro in peripheral blood lymphocytes from 20 polygenic hypercholesterolemic patients prior to their recruitment into a rigorous dietary and pharmacological treatment program. The patients in the diet program demonstrated significant beneficial changes in plasma, LDL and HDL cholesterol concentrations. After 12 weeks, those patients who had not had reductions in LDL cholesterol to within the reference range, had cholestyramine and/or bezafibrate supplements to the diet for a further six weeks. The beneficial trends continued. The LDL receptor values correlated well with pre-treatment LDL cholesterol and plasma apoprotein B concentrations (r = -0.472, P less than 0.01 and r = -0.526, P less than 0.01, respectively) and with the percentage change induced by diet (r = 0.510, P less than 0.01 and r = 0.480, P less than 0.01, respectively) and by diet supplemented with bezafibrate and cholestyramine (r = 0.634, P less than 0.05 and r = 0.629, P less than 0.05, respectively). In polygenic hypercholesterolemic patients in whom LDL receptor activity is high, treatment with diet alone may be sufficient whereas those with low receptor activity would require specific pharmacological intervention.