The effect of skim milk from cows immunized against a variety of human intestinal bacteria on serum cholesterol concentrations was examined in 11 patients with primary hypercholesterolemia in a 24-wk, randomized, double-blind, placebo-controlled, crossover study. After a 4-wk baseline period, patients were treated for 8 wk either with skim milk from immunized cows (active) or with control skim milk (placebo) followed by an 8-wk period with the treatment order reversed. Eight weeks of active treatment with skim milk from immunized cows reduced serum total cholesterol concentrations by 0.52 +/- 0.59 mmol/L (mean +/- SD; P less than 0.025), or 8%, LDL cholesterol by 0.16 +/- 0.59 mmol/L (NS), or 4%, and the atherogenic index (total cholesterol/HDL cholesterol) by 0.42 +/- 1.85 (P less than 0.05), or 8%, compared with the placebo treatment. Reversal of the favorable development occurred upon cessation of active treatment. We conclude that daily supplementation of a normal diet with skim milk from immunized cows can result in a significant reduction of elevated blood cholesterol concentrations.