Twenty subjects with familial hypercholesterolemia (12 Type IIa and 8 Type IIb), previously treated with Colestipol for 16 months, were subjected to therapy with Colestipol (15 g/day) + clofibrate (2 g/day) for 15 months. During the second treatment period these patients continued to follow the isocaloric hypocholesterolemic diet initiated during the original trial. In Type IIa patients, the association of these drugs enhanced the decrease in plasma cholesterol levels. The total mean decrease was -40 +/- 17 mg/dl (P less than 0.05). In Type IIb patients, on the other hand, the association of clofibrate with Colestipol induced an increase in plasma cholesterol levels. The total mean increase was +24 +/- 7 mg/dl (P less than 0.05). A markedly significant decrease in plasma triglyceride levels was observed in this group (- 107 +/- 30; P less than 0.01). These results seem to indicate that, in Type IIa, clofibrate increased the resin's hypocholesterolemic effect. In Type IIb, on the other hand, the association of these drugs did not seem to be indicated since a marked hypotriglyceridemic effect was accompanied by an increase in plasma cholesterol levels. These results are briefly discussed in the light of recent data obtained on the effects of Colestipol and clofibrate on lipoprotein metabolism.