AbstractLimonin 17‐β‐d‐glucopyranoside, nomilin 17‐β‐d‐glucopyranoside, and nomilinic acid 17‐β‐d‐glucopyranoside, three limonoid glucosides isolated from oranges, were tested for cancer chemopreventive activity. Eighty female Syrian hamsters were divided into four equal groups. The left buccal pouches of the animals in each group were pretreated topically with two applications of water (Group I) or a 3.5% solution of limonin 17‐β‐d‐glucopyranoside (Group II), nomilin 17‐β‐d‐glucopyranoside (Group III), or nomilinic acid 17‐β‐d‐gluco‐pyranoside (Group IV). After this initial treatment, the left buccal pouches of 16 hamsters from each group were painted five times per week. Two or three times per week the pouches were treated with a 0.5% solution of the carcinogen 7,12‐di‐methylbenz[a]anthracene (DMBA) dissolved in mineral oil. On alternate days, the pouches were treated with water (Group I) or a 3.5% solution of limonin 17‐β‐d‐glucopyranoside (Group II), nomilin 17‐β‐d‐glucopyranoside, or nomilinic acid 17‐β‐d‐glucopyranoside. The 16 remaining animals were used as controls. These hamsters were treated five times per week, one day with mineral oil and the next with either water (Group I) or one of the 3.5% solutions of the limonoid glucosides (Groups II‐IV). After 15 weeks (71 applications), the hamsters were killed. Multiple tumors were common in the animals treated with DMBA; however, the animals treated with limonin 17‐β‐d‐glucopyranoside exhibited a 55% decrease in average tumor burden. Further comparisons between Groups I and II showed that this reduction in tumor burden was mainly due to a decrease in tumor mass. The results for Groups III and IV showed that nomilin 17‐β‐d‐glucopyranoside and nomilinic acid 17‐β‐d‐glucopyranoside were ineffective as inhibitors of DMBA‐induced buccal pouch neoplasia.