During treatment with probucol at the dose of 1 g per day, the mean reduction in low density lipoprotein (LDL) cholesterol concentration was 11.2% in polygenic hypercholesterolaemia (n = 9) and 9.4% in heterozygous familial hypercholesterolaemia (n = 6). However, there was marked heterogeneity of response: in seven of the patients with polygenic hypercholesterolaemia who had in common moderate elevation of LDL cholesterol (5.3-6.4 mmol/1), the reduction ranged from 13 to 40% (mean, 23%). In two of this group the change in LDL concentration was associated with a decrease in LDL apolipoprotein B synthetic rate. Of the patients with familial hypercholesterolaemia one showed a 33% reduction in LDL cholesterol, and one a 13% reduction. Total high density lipoprotein (HDL) cholesterol concentration tended to decrease during treatment. This reflected a reduction of the cholesterol concentration in the HDL3 subclass; HDL2 cholesterol remaining unchanged. Plasma triglyceride and very low density lipoprotein cholesterol were unaffected by probucol. The drug was well tolerated with only one patient complaining of severe diarrhoea, and two of mild and transient diarrhoea. No clinically significant changes occurred in serial resting electrocardiograms. Thus, probucol appears to be a useful drug for the treatment of most patients with polygenic hypercholesterolaemia, and of some patients with heterozygous familial hypercholesterolaemia.