We have carried out in vitro and animal studies to determine the cholesterol lowering efficacy of activated charcoals vs. cholestyramine. In the in vitro studies, we determined the adsorption capacity (Qm) of cholestyramine and activated charcoals for cholesterol in glacial acetic acid. Mean (+/- SD) Qm's (mg cholesterol adsorbed/gm dry sorbent) decreased in the order Super Char highly activated charcoal (277 +/- 121), Norit USP XX charcoal (33 +/- 10), Acta-Char charcoal (26 +/- 4), Mallinckrodt USP charcoal (26 +/- 10), Norit A charcoal (22 +/- 4) and cholestyramine (0). For the bile salt sodium desoxycholate in ammonia: sodium bicarbonate, pH 8.2, the Qm with cholestyramine was 4641 +/- 2669 and with Super Char was 2814 +/- 667 (p = 0.11). We then contrasted the effect of cholestyramine (1%, added to the diet) and Super Char (1% or 2%) on plasma cholesterol concentrations in rabbits made hypercholesterolemic with a diet containing casein. The percent reductions were 61 in one rabbit fed cholestyramine, 61 and 67 in two rabbits fed 1% Super Char, and 90 in one rabbit fed 2% Super Char. In WHHL homozygous rabbits, reductions in plasma cholesterol from pre-treatment and post-treatment levels, respectively, averaged 52% and 38% with 2% cholestyramine (2 animals), 70% and 43% with 2% Super Char (2 animals), and 70% and 63% with 4% Super Char (3 animals). The effectiveness of cholestyramine in animals that lack functional cellular receptors for low density lipoprotein was unexpected. Super Char charcoal appears to be an effective hypocholesterolemic agent, warranting study in man.