Rabbits become hypercholesterolemic when transferred from commercial feed to a low fat, cholesterol-free semisynthetic diet. The role of different dietary components in mediating this effect was investigated by varying the composition of the semisynthetic diet and of the commerical feed. Addition of alfalfa to the semisynthetic diet prevented the normal hypercholesterolemic response, but other plant products, including several with high fibre content, were ineffective. Increasing the content of powdered cellulose appeared to enhance the response. A commercially formulated diet in which the alfalfa and soybean meal components were replaced by ground corn and oats did not produce a significant elevation of plasma cholesterol. Substitution of different sugars or starches for the dextrose in the semisynthetic diet gave variable results, but of those tested, only potato starch prevented the hypercholesterolemia. The type of protein used in the semisynthetic diet had a marked influence on the level of plasma cholesterol. Semisynthetic diets containing proteins from animal sources gave higher plasma cholesterol levels than those containing proteins from plant sources. Very low levels were obtained with a low choline semisynthetic diet containing soy protein isolate, and supplementation with choline and methionine only raised the level to that normally obtained with commercial feed. Replacement of the salt mixture in the semisynthetic diet by one specially recommended for rabbits made no significant difference to the hypercholesterolemic response. Prevention of coprophagy did not significantly affect plasma cholesterol levels in rabbits on either commerical or semisynthetic diets. Growth performance was generally better on commercial feed than on semisynthetic diets but there was no direct correlation between weight gain and level of plasma cholesterol in rabbits on the different semisynthetic diets.