Limited information is available on lignan metabolism and tissue distribution between sexes and the effects of prolonged lignan exposure on tissue concentrations. In the present study, excretion and tissue distribution of lignans were compared after 1 d and 7 d administration of flaxseed lignan secoisolariciresinol diglycoside (SDG) in male and female rats. Sprague-Dawley rats were daily gavaged per os with 3H-SDG (3.7 kBq/g body weight (bwt)) and unlabelled SDG (5.3 microg/g bwt). Urine, faeces, serum and tissues (liver, kidneys, bladder, spleen, lungs, brain, thymus, heart, muscle, adipose, mammary gland, ovaries, vagina, uterus, testis, seminal vesicles, coagulating glands and ventral prostate) were collected at 0, 12 and 24 h after a single lignan dose or after the last dose of 7 d exposure. The sample total lignan content was measured as radioactivity by liquid scintillation counting. In both sexes, majority of radioactivity was excreted in faeces (40-83%) and urine (1.2-5.2%). 3H-SDG administration increased radioactivity in all tissues at all time points, and the levels were further increased after prolonged SDG exposure. Liver contained majority of the tissue lignans (48-56%) in both sexes after both exposure regimens. After prolonged SDG exposure, the serum lignan concentrations had reached a plateau which was approximately 4-fold of that of acute exposure, whereas in both sexes, concentrations in skin and kidneys still increased, indicating tissue accumulation. After prolonged exposure, females had higher lignan concentrations in heart and thymus at all time points, demonstrating sex-related differences in lignan tissue distribution and the possibility for sex-specific treatment responses. These findings facilitate identification of target tissues for local lignan actions in vivo.