Dietary hypocholesterolemic adjuncts may have a beneficial role in the prevention and treatment of cholesterol gallstones (CGS). In this investigation, fenugreek (Trigonella foenum-graecum) seed was evaluated for this potential on the experimental induction of CGS in laboratory mice. CGS was induced by maintaining mice on a lithogenic diet (0.5% cholesterol) for 10 weeks. Fenugreek seed powder was included at 5%, 10%, and 15% of this lithogenic diet. Dietary fenugreek significantly lowered the incidence of CGS in these mice; the incidence was 63%, 40%, and 10% in the 5%, 10%, and 15% fenugreek groups, respectively, compared with 100% in the lithogenic control. The antilithogenic influence of fenugreek is attributable to its hypocholesterolemic effect. Serum cholesterol level was decreased by 26%-31% by dietary fenugreek, while hepatic cholesterol was lowered by 47%-64% in these high cholesterol-fed animals. Biliary cholesterol was 8.73-11.2 mmol/L as a result of dietary fenugreek, compared with 33.6 mmol/L in high-cholesterol feeding without fenugreek. Cholesterol saturation index in bile was reduced to 0.77-0.99 in fenugreek treatments compared with 2.57 in the high-cholesterol group. Thus, fenugreek seed offers health-beneficial antilithogenic potential by virtue of its favourable influence on cholesterol metabolism.