A significant reduction in plasma high density lipoprotein (HDL) cholesterol is a recognised consequence of treatment with probucol. By contrast, fibrate therapy in general has the opposite effect. We report two cases where the combination of probucol and a fibrate led to profoundly reduced plasma levels of HDL cholesterol associated with very low levels of apolipoprotein A-I (apoA-I). In the first, bezafibrate was added to probucol, and in the second, probucol added to a combination of simvastatin and fenofibrate. In both cases, plasma levels of HDL and apoA-I returned towards normal after discontinuation of one or both drugs, indicating that the reduction was reversible.