Mammalian lignans from colonic bacterial action on secoisolariciresinol diglycoside (SDG) may mediate the anticarcinogenic effect of prolonged SDG feeding in rats. To elucidate lignan bioactivity, our objective was to determine 3H-SDG disposition in rats with acute or chronic SDG treatment over 48 h. After food deprivation overnight, female Sprague-Dawley rats (70-72 d old) were given a single gavage of 3H-SDG (3.7 kBq/g body weight) either immediately (acute, n = 12) or after 10 d of gavage with 1.5 mg unlabeled SDG/d (chronic, n = 12). Rats were killed at 12, 24, 36 and 48 h after gavage, and samples collected and analyzed for radioactivity by liquid scintillation counting. Radioactivity was 1- to 16-fold higher at 12 vs. 48 h for tissues, blood and gastrointestinal contents (P < 0.05). By 48 h, >80% of the recovered dose was excreted in both groups (feces > 50%, urine = 28-32%). Tissue radioactivity was highest (by 0.5- to 176-fold) in the cecum (P < 0.05). Levels in the liver, kidney and uterus (12 h) were 0.2- to 7.5-fold higher than in other nongastrointestinal tissues. At 12 h, fecal radioactivity was negligible, and cecal content, liver and adipose radioactivity were one- to threefold greater in rats with chronic SDG exposure than in those acutely exposed (P < 0.05). Blood radioactivity, present mostly in the plasma fraction (0.4% of dose), suggested that lignan concentrations could be 3000 times higher than peak estrogen levels in rats. Thus, SDG metabolites accumulated in the liver, kidney, intestinal tissues and uterus. Chronic SDG exposure delayed fecal excretion while increasing liver and adipose lignan levels.